42 research outputs found

    Comparative evaluation of hydrogen peroxide sporicidal efficacy bdifferent standard test methods

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    Background and Objectives: There are different sporicidal standard tests with various specifications to deal with products that are claimed for sporicidal activity. The aim of this study was to compare the 7 H2O2 sporicidal efficacy against Bacillus subtilis spores using different standard test methods. Materials and Methods: The 7 H2O2 sporicidal efficacy against Bacillus subtilis spores was determined according to the AOAC MB-15-04 standard of carrier test and two standard suspension tests (BS EN 13704, AFNOR NF 72-230) in both clean and dirty conditions and by using different interfering substances including bovine serum albumin, yeast extract and skimmed milk. Results: The results of suspension tests with 3 � 105 and 2 � 107 CFU/ml of B. subtilis spore concentration demonstrated that the higher spore counts lead to lower efficacy of 7 H2O2. Also, the sporicidal activity of 7 H2O2 was reduced in the presence of interfering substances. Bovine serum albumin, yeast, and skimmed milk showed similar interfering effects in suspension test with 3 � 105 CFU/ml. While, in suspension tests with higher initial spore count (2 � 107 CFU/ml) severity of interfering effects were intensified and distinct. Our results indicated that the carrier sporicidal test in comparison with suspension tests required more contact time to kill B. subtilis spores. Conclusion: The results of this study showed that it is reasonable to use interfering substances and inoculated carriers in accordance with actual conditions of product usage in a sporicidal test. Interfering substances may reduce the contact surface between H2O2 and test spores; therefore, the sporicidal efficacy of H2O2 was diminished. So applying suspension test in clean condition to verify the claim of sporicidal activity is strongly discouraged. © 2020, Tehran University of Medical Science. All rights reserved

    A review of potential suggested drugs for coronavirus disease (COVID-19) treatment

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    The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79 and 50 genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they are not specific and targeted. Therefore, several drugs have been investigated for their efficacy and safety in the treatment of COVID-19; most of them are undergoing clinical trials. This article summarizes clinical investigations of potential therapeutic drugs used as COVID-19 therapy. Subsequently, it prepares a pattern of results and therapeutic targets to help further experiment designs. We have investigated drugs as classified in the following three groups; 1) The drugs which computationally showed effectiveness (in silico) but needed further lab confirmations; 2) Emetine, Teicoplanin, and Nelfinavir have shown effectiveness in vitro; 3) The drugs currently under clinical trial. © 2021 Elsevier B.V

    A review of potential suggested drugs for coronavirus disease (COVID-19) treatment

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    The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79 and 50 genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they are not specific and targeted. Therefore, several drugs have been investigated for their efficacy and safety in the treatment of COVID-19; most of them are undergoing clinical trials. This article summarizes clinical investigations of potential therapeutic drugs used as COVID-19 therapy. Subsequently, it prepares a pattern of results and therapeutic targets to help further experiment designs. We have investigated drugs as classified in the following three groups; 1) The drugs which computationally showed effectiveness (in silico) but needed further lab confirmations; 2) Emetine, Teicoplanin, and Nelfinavir have shown effectiveness in vitro; 3) The drugs currently under clinical trial. © 2021 Elsevier B.V

    Rapamycin-loaded, capryol� 90 and oleic acid mediated nanoemulsions: Formulation development, characterization and toxicity assessment

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    This study was planned to explore the capability of nanoemulsions (NEs) consisting of Capryol� 90 and oleic acid for the delivery of rapamycin (RAP). Permeability and cytotoxicity of RAP-loaded NEs were also inspected. Pseudo-ternary phase diagrams were created with oleic acid and Capryol� 90 (as oil phase) and four surfactants and co-surfactants at various weight ratios (Rsm). Selected NEs from O/W region on the phase diagrams with the drug concentration of 1 mg/mL, were prepared via the spontaneous emulsification technique, characterized for particle size and subjected to stability tests at various temperatures over 9-12 months. Cumulative drug release was determined for a period of 48 h using a dialysis sac. The assay of RAP was determined using HPLC technique. Cytotoxicity of NEs was evaluated by MTT assay on breast cancer cell line, namely SKBR-3. The permeability of RAP-loaded NEs across Caco-2 monolayers was assessed by measurement of TEER (transepithelial electrical resistance) value. The intracellular uptake of coumarin 6-loaded NEs by SKBR-3 cells was also investigated using florescence microscopy. NEs containing oleic acid/Tween 20/propylene glycol, Capryol� 90/Tween 20/iso-propanol, and Capryol� 90/Cremophor® RH40/Transcutol® P showed more cytotoxicity and permeability compared with the RAP methanolic solution. The minimum toxic concentration of RAP in NE formulations was found to be 7.5 µg/mL. The highest intracellular uptake was observed for the NE composed of Capryol� 90/Tween 20/iso-propanol which was in consistent with the results obtained from cytotoxicity and permeability tests. The overall results implicated that this novel carrier was effective for enhancing RAP permeation in Caco-2 cell membrane along with enhancement of cytotoxicity. © 2018, Iranian Journal of Pharmaceutical Research. All rights reserved

    The benefits of folic acid-modified gold nanoparticles in CT-based molecular imaging: radiation dose reduction and image contrast enhancement

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    X-ray computed tomography (CT) requires an optimal compromise between image quality and patient dose. While high image quality is an important requirement in CT, the radiation dose must be kept minimal to protect the patients from ionizing radiation-associated risks. The use of probes based on gold nanoparticles (AuNPs) along with active targeting ligands for specific recognition of cancer cells may be one of the balanced solutions. Herein, we report the effect of folic acid (FA)-modified AuNP as a targeted nanoprobe on the contrast enhancement of CT images as well as its potential for patient dose reduction. For this purpose, nasopharyngeal KB cancer cells overexpressing FA receptors were incubated with AuNPs with and without FA modification and imaged in a CT scanner with the following X-ray tube parameters: peak tube voltage of 130�KVp, and tube current�time products of 60, 90, 120, 160 and 250�mAs. Moreover, in order to estimate the radiation dose to which the patient was exposed during a head CT protocol, the CT dose index (CTDI) value was measured by an X-ray electrometer by changing the tube current�time product. Raising the tube current�time product from 60 to 250�mAs significantly increased the absorbed dose from 18�mGy to 75�mGy. This increase was not associated with a significant enhancement of the image quality of the KB cells. However, an obvious increase in image brightness and CT signal intensity (quantified by Hounsfield units HU) were observed in cells exposed to nanoparticles without any increase in the mAs product or radiation dose. Under the same Au concentration, KB cells exposed to FA-modified AuNPs had significantly higher HU and brighter CT images than those of the cells exposed to AuNPs without FA modification. In conclusion, FA-modified AuNP can be considered as a targeted CT nanoprobe with the potential for dose reduction by keeping the required mAs product as low as possible while enhancing image contrast. © 2017 Informa UK Limited, trading as Taylor & Francis Grou

    Phenotypic and Genome-Wide Analysis of an Antibiotic-Resistant Small Colony Variant (SCV) of Pseudomonas aeruginosa

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    Small colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch.One SCV (termed PAO-SCV) was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence of large colonies with a frequency of 10(-5) on media without antibiotics while it was stably maintained in presence of gentamicin. PAO-SCV showed a delayed growth, defective motility, and strongly reduced levels of the quorum sensing Pseudomonas quinolone signal (PQS). Whole genome expression analysis further suggested a multi-layered antibiotic resistance mechanism, including simultaneous over-expression of two drug efflux pumps (MexAB-OprM, MexXY-OprM), the LPS modification operon arnBCADTEF, and the PhoP-PhoQ two-component system. Conversely, the genes for the synthesis of PQS were strongly down-regulated in PAO-SCV. Finally, genomic analysis revealed the presence of mutations in phoP and phoQ genes as well as in the mexZ gene encoding a repressor of the mexXY and mexAB-oprM genes. Only one mutation occurred only in REV, at nucleotide 1020 of the tufA gene, a paralog of tufB, both encoding the elongation factor Tu, causing a change of the rarely used aspartic acid codon GAU to the more common GAC, possibly causing an increase of tufA mRNA translation. High expression of phoP and phoQ was confirmed for the SCV variant while the revertant showed expression levels reduced to wild-type levels.By combining data coming from phenotypic, gene expression and proteome analysis, we could demonstrate that resistance to aminoglycosides in one SCV mutant is multifactorial including overexpression of efflux mechanisms, LPS modification and is accompanied by a drastic down-regulation of the Pseudomonas quinolone signal quorum sensing system

    S‌U‌G‌G‌E‌S‌T‌I‌O‌N‌S T‌O R‌E‌M‌O‌V‌E T‌H‌E C‌O‌N‌T‌I‌N‌U‌I‌T‌Y P‌L‌A‌T‌E‌S O‌F B‌O‌X C‌O‌L‌U‌M‌N‌S

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    T‌h‌r‌e‌e m‌a‌i‌n p‌a‌r‌a‌m‌e‌t‌e‌r‌s i‌n s‌t‌e‌e‌l m‌o‌m‌e‌n‌t-r‌e‌s‌i‌s‌t‌i‌n‌g c‌o‌n‌n‌e‌c‌t‌i‌o‌n (M‌R‌C) d‌e‌s‌i‌g‌n a‌r‌e; s‌t‌i‌f‌f‌n‌e‌s‌s, s‌t‌r‌e‌n‌g‌t‌h, a‌n‌d d‌u‌c‌t‌i‌l‌i‌t‌y. T‌h‌e r‌e‌s‌p‌o‌n‌s‌e o‌f t‌h‌e b‌e‌a‌m-t‌o-c‌o‌l‌u‌m‌n c‌o‌n‌n‌e‌c‌t‌i‌o‌n‌s i‌s s‌t‌r‌o‌n‌g‌l‌y a‌f‌f‌e‌c‌t‌e‌d b‌y t‌h‌e p‌a‌n‌e‌l z‌o‌n‌e. W‌i‌d‌e e‌x‌p‌e‌r‌i‌m‌e‌n‌t‌a‌l a‌n‌d a‌n‌a‌l‌y‌t‌i‌c‌a‌l s‌t‌u‌d‌i‌e‌s h‌a‌v‌e b‌e‌e‌n c‌a‌r‌r‌i‌e‌d o‌u‌t i‌n o‌r‌d‌e‌r t‌o e‌x‌a‌m‌i‌n‌e t‌h‌e b‌e‌h‌a‌v‌i‌o‌r o‌f p‌a‌n‌e‌l z‌o‌n‌e N‌o‌r‌t‌h‌r‌i‌d‌g‌e (1994) a‌n‌d K‌o‌b‌e (1995) e‌a‌r‌t‌h‌q‌u‌a‌k‌e‌s s‌h‌o‌w‌e‌d t‌h‌a‌t e‌x‌c‌e‌s‌s‌i‌v‌e s‌h‌e‌a‌r d‌i‌s‌t‌o‌r‌t‌i‌o‌n‌s c‌o‌u‌l‌d c‌r‌e‌a‌t‌e b‌r‌i‌t‌t‌l‌e r‌u‌p‌t‌u‌r‌e‌s a‌t t‌h‌e w‌e‌l‌d‌s o‌f b‌e‌a‌m-t‌o-c‌o‌l‌u‌m‌n c‌o‌n‌n‌e‌c‌t‌i‌o‌n. T‌h‌e r‌e‌s‌u‌l‌t‌s o‌b‌t‌a‌i‌n‌e‌d f‌r‌o‌m t‌h‌e‌s‌e E‌a‌r‌t‌h‌q‌u‌a‌k‌e‌s h‌a‌v‌e b‌e‌e‌n r‌e‌f‌l‌e‌c‌t‌e‌d i‌n t‌h‌e s‌u‌b‌s‌e‌q‌u‌e‌n‌t c‌h‌a‌n‌g‌e‌s p‌r‌o‌p‌o‌s‌e‌d t‌o t‌h‌e d‌e‌s‌i‌g‌n a‌p‌p‌r‌o‌a‌c‌h i‌n t‌h‌e A‌m‌e‌r‌i‌c‌a‌n a‌n‌d E‌u‌r‌o‌p‌e‌a‌n c‌o‌d‌e‌s. A‌I‌S‌C p‌r‌e‌q‌u‌a‌l‌i‌f‌i‌e‌d c‌o‌n‌n‌e‌c‌t‌i‌o‌n‌s c‌a‌n b‌e u‌s‌e‌d f‌o‌r c‌o‌l‌u‌m‌n‌s i‌f h‌o‌r‌i‌z‌o‌n‌t‌a‌l c‌o‌n‌t‌i‌n‌u‌i‌t‌y p‌l‌a‌t‌e‌s a‌r‌e u‌s‌e‌d i‌n‌s‌i‌d‌e t‌h‌e c‌o‌l‌u‌m‌n. T‌h‌e u‌s‌e o‌f i‌n‌t‌e‌r‌n‌a‌l h‌o‌r‌i‌z‌o‌n‌t‌a‌l c‌o‌n‌t‌i‌n‌u‌i‌t‌y p‌l‌a‌t‌e‌s a‌s t‌h‌i‌c‌k a‌s t‌h‌e b‌e‌a‌m f‌l‌a‌n‌g‌e p‌l‌a‌t‌e‌s o‌r s‌t‌i‌f‌f‌e‌n‌e‌r‌s h‌a‌s b‌e‌e‌n e‌m‌p‌h‌a‌s‌i‌z‌e‌d b‌y F‌E‌M‌A355-D, t‌o p‌r‌o‌v‌i‌d‌e a g‌o‌o‌d s‌e‌i‌s‌m‌i‌c p‌e‌r‌f‌o‌r‌m‌a‌n‌c‌e f‌o‌r b‌e‌a‌m-t‌o-c‌o‌l‌u‌m‌n c‌o‌n‌n‌e‌c‌t‌i‌o‌n‌s. C‌o‌n‌t‌i‌n‌u‌i‌t‌y p‌l‌a‌t‌e‌s a‌r‌e w‌e‌l‌d‌e‌d t‌o t‌h‌e c‌o‌l‌u‌m‌n w‌e‌b a‌n‌d f‌l‌a‌n‌g‌e a‌t t‌h‌e l‌e‌v‌e‌l o‌f t‌e‌n‌s‌i‌o‌n a‌n‌d c‌o‌m‌p‌r‌e‌s‌s‌i‌o‌n b‌e‌a‌m f‌l‌a‌n‌g‌e‌s. P‌e‌r‌f‌o‌r‌m‌i‌n‌g t‌h‌e‌s‌e p‌l‌a‌t‌e‌s i‌n c‌o‌n‌n‌e‌c‌t‌i‌o‌n w‌i‌t‌h I b‌e‌a‌m‌s t‌o w‌i‌d‌e f‌l‌a‌n‌g‌e c‌o‌l‌u‌m‌n‌s i‌s e‌a‌s‌y a‌n‌d p‌o‌s‌s‌i‌b‌l‌e. T‌h‌r‌e‌e f‌a‌c‌e‌s o‌f c‌o‌n‌t‌i‌n‌u‌i‌t‌y p‌l‌a‌t‌e‌s i‌n m‌o‌m‌e‌n‌t f‌r‌a‌m‌e c‌o‌n‌n‌e‌c‌t‌i‌o‌n w‌i‌t‌h I s‌e‌c‌t‌i‌o‌n b‌e‌a‌m a‌n‌d B‌o‌x c‌o‌l‌u‌m‌n s‌e‌c‌t‌i‌o‌n c‌a‌n w‌e‌l‌d C‌J‌P g‌r‌o‌o‌v‌e w‌e‌l‌d b‌u‌t i‌n t‌h‌e c‌o‌n‌n‌e‌c‌t‌i‌o‌n f‌o‌r‌t‌h f‌a‌c‌e h‌a‌s m‌a‌n‌y d‌i‌f‌f‌i‌c‌u‌l‌t‌i‌e‌s. T‌h‌i‌s s‌t‌u‌d‌y f‌i‌r‌s‌t d‌i‌s‌c‌u‌s‌s‌e‌s t‌h‌e e‌f‌f‌e‌c‌t‌s o‌f c‌o‌n‌t‌i‌n‌u‌i‌t‌y p‌l‌a‌t‌e i‌n I b‌e‌a‌m t‌o B‌o‌x s‌e‌c‌t‌i‌o‌n m‌o‌m‌e‌n‌t f‌r‌a‌m‌e c‌o‌n‌n‌e‌c‌t‌i‌o‌n w‌i‌t‌h t‌o‌p a‌n‌d b‌o‌t‌t‌o‌m p‌l‌a‌t‌e (W‌F‌P) t‌h‌e‌n r‌e‌c‌o‌m‌m‌e‌n‌d n‌e‌w d‌e‌t‌a‌i‌l‌s f‌o‌r e‌l‌i‌m‌i‌n‌a‌t‌i‌n‌g c‌o‌n‌t‌i‌n‌u‌i‌t‌y p‌l‌a‌t‌e. S‌t‌u‌d‌i‌e‌s h‌a‌v‌e s‌h‌o‌w‌n t‌h‌a‌t t‌h‌e e‌l‌i‌m‌i‌n‌a‌t‌i‌o‌n o‌f c‌o‌n‌t‌i‌n‌u‌i‌t‌y p‌l‌a‌t‌e i‌n W‌F‌P c‌o‌n‌n‌e‌c‌t‌i‌o‌n‌s d‌e‌c‌r‌e‌a‌s‌e‌d l‌o‌a‌d‌i‌n‌g c‌a‌p‌a‌c‌i‌t‌y, r‌i‌g‌i‌d‌i‌t‌y a‌n‌d e‌n‌e‌r‌g‌y a‌b‌s‌o‌r‌p‌t‌i‌o‌n a‌b‌o‌u‌t 43, 58 a‌n‌d 35 p‌e‌r‌c‌e‌n‌t r‌e‌s‌p‌e‌c‌t‌i‌v‌e‌l‌y. I‌n a‌d‌d‌i‌t‌i‌o‌n c‌o‌n‌n‌e‌c‌t‌i‌o‌n‌s a‌r‌e p‌r‌o‌p‌o‌s‌e‌d i‌n t‌h‌i‌s s‌t‌u‌d‌y f‌o‌r W‌F‌P c‌o‌n‌n‌e‌c‌t‌i‌o‌n w‌i‌t‌h i‌n‌t‌e‌r‌n‌a‌l c‌o‌n‌t‌i‌n‌u‌i‌t‌y p‌l‌a‌t‌e‌s, o‌n a‌v‌e‌r‌a‌g‌e l‌e‌a‌d‌i‌n‌g t‌o r‌e‌d‌u‌c‌t‌i‌o‌n i‌n l‌o‌a‌d‌i‌n‌g c‌a‌p‌a‌c‌i‌t‌y, r‌i‌g‌i‌d‌i‌t‌y a‌n‌d e‌n‌e‌r‌g‌y a‌b‌s‌o‌r‌p‌t‌i‌o‌n a‌b‌o‌u‌t 8.9, 11.6 a‌n‌d 9.2 p‌e‌r‌c‌e‌n‌t r‌e‌s‌p‌e‌c‌t‌i‌v‌e‌l‌y. M‌o‌r‌e‌o‌v‌e‌r, I s‌h‌a‌p‌e c‌o‌n‌t‌i‌n‌u‌i‌t‌y p‌l‌a‌t‌e h‌a‌s b‌e‌t‌t‌e‌r p‌e‌r‌f‌o‌r‌m‌a‌n‌c‌e t‌h‌a‌n o‌t‌h‌e‌r t‌w‌o m‌e‌n‌t‌i‌o‌n‌e‌d c‌o‌n‌n‌e‌c‌t‌i‌o‌n‌s

    Synergistic anti-tumor effects of Liraglutide, a glucagon-like peptide-1 receptor agonist, along with Docetaxel on LNCaP prostate cancer cell line

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    Docetaxel is a first line chemotherapy agent, which stabilizes microtubules in metastatic prostate cancer (PCa). Resistance to Docetaxel and its side effects remain as obstacle for its efficacy in monotherapy. Recently, combination with novel adjuvants have been emerged as a beneficial alternative strategy, which targets multiple important pathways and also requires lower therapeutic dosage, proposing as a strategy to overcome drug resistance. This study investigated whether Liraglutide, a Glucagon Like Peptide-1 Receptor agonist, can reinforce the effect of Docetaxel on LNCaP prostate cancer cell line. Cells were treated by Liraglutide and Docetaxel, alone and in combination. Cytotoxicity was evaluated by MTT assay. Compusyn and Combenefit softwares were used in order to evaluate synergistic efficacy. Apoptosis was determined by Cell cycle analysis and Annexin-V/Propidium iodide staining through flow cytometry. However, the mRNA level of pro-apoptotic gene �Bax� and anti-apoptotic �Bcl-2� were evaluated by quantitative Real-Time PCR. Also, phosphorylation level of ERK1/2 and AKT proteins was investigated by western blotting technique. The results showed that Docetaxel and Liraglutide decreased the viability of LNCaP cells synergistically, caused cell cycle arrest and induced apoptosis potentially. The key proteins� evaluation in ERK/MAPK and AKT/PI3K pathways revealed a significant reduction in phosphorylation level of cells exposed to combination of drugs. Our results suggest that, the combination of Liraglutide and Docetaxel could be considered as a potent strategy in enhancing the efficacy of treatment, decreasing the Docetaxel therapeutic dose and thereby lowering systemic toxicities and resistances. © 2020 Elsevier B.V
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