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Comparison of three dimensional synergistic analyses of percentage versus logarithmic data in antiviral studies.

ABSTRACT: Cell culture antiviral experiments were conducted in order to understand the relationship between percentage data generated by plaque reduction (PR) and logarithmic data derived by virus yield reduction (VYR) assays, using three-dimensional MacSynergy II software. The relationship between percentage and logarithmic data has not been investigated previously. Interpretation of drug-drug interactions is based on a Volume of Synergy (VS) calculation, which can be positive (synergy), negative (antagonistic), or neutral (no or minimal interaction). Interactions of two known inhibitors of vaccinia virus replication, cidofovir and 6-azauridine, used in combination by PR assay yielded a VS value of 265, indicative of strong synergy. By VYR, the VS value was only 37, or weak synergy using the same criterion, even though profound log10 reductions in virus titer occurred at multiple drug combinations. These results confirm that the differences in VS values is dependent of the measurement scale, and not that the degree of synergy differed between the assays. We propose that for logarithmic data, the calculated VS values will be lower for significant synergy and antagonism and that volumes of >10 ?M2log10 PFU/ml (or other units such as ?M2log10 genomic equivalents/ml or ?M2log10 copies/ml) and <-10 ?M2log10 PFU/ml are likely to be indicative of strong synergy and strong antagonism, respectively. Data presented here show that the interaction of cidofovir and 6-azauridine was strongly synergistic in vitro.

SUBMITTER: Smee DF

PROVIDER: S-EPMC5575975 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Comparison of three dimensional synergistic analyses of percentage versus logarithmic data in antiviral studies.

Smee Donald F DF Prichard Mark N MN

Antiviral research 20170701

Cell culture antiviral experiments were conducted in order to understand the relationship between percentage data generated by plaque reduction (PR) and logarithmic data derived by virus yield reduction (VYR) assays, using three-dimensional MacSynergy II software. The relationship between percentage and logarithmic data has not been investigated previously. Interpretation of drug-drug interactions is based on a Volume of Synergy (VS) calculation, which can be positive (synergy), negative (antago ...[more]

PMID: 28676302

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Project description:Histological analysis is considered to be the gold standard method of evaluating osseointegration around a bone-implant. However, this method requires invasive specimen preparation and is capable of representing only one plane. By comparison, micro-computed tomography (μCT) is a fast and convenient method that offers three-dimensional information but is hampered by problems related to resolution and artifacts, making it a supplementary method for osseointegration analysis. To verify the reliability of μCT for osseointegration evaluation, this animal model study compared bone-to-implant contact (BIC) ratios obtained by the gold standard histomorphometric method with those obtained by the μCT method, using a rabbit tibia implant model. A sandblasted, large-grit, acid-etched (SLA) implant and a machined surface implant were inserted into each tibia of two rabbits (giving eight implants in total). Bone-implant specimens were analyzed using μCT with a spiral scan technique (SkyScan 1275) and histological sections were prepared thereafter. Three-dimensional (3D) reconstructed μCT data and four two-dimensional (2D) μCT sections, including one section corresponding to the histologic section and three additional sections rotated 45°, 90°, and 135°, were used to calculate the BIC ratio. The Pearson's test was used for correlation analysis at a significance level of 0.05. The histomorphometric BIC and the 2D-μCT BIC showed strong correlation (r = 0.762, P = 0.046), whereas the histomorphometric BIC and 3D-μCT BIC did not (r = -0.375, P = 0.385). However, the mean BIC value of three or four 2D-μCT sections showed a strong correlation with the 3D-μCT BIC (three sections: r = 0.781, P = 0.038; four sections: r = 0.804, P = 0.029). The results of this animal model study indicate that μCT can be used to complement the histomorphometric method in bone-implant interface analyses. With the limitations of this study, 3D-μCT analysis may even have a superior aspect in that it eliminates random variables that arise as a consequence of the selected cutting direction.

Project description:Purpose To test and compare the association between radiologic measurements of lesion diameter, volume, and enhancement on baseline magnetic resonance (MR) images with overall survival and tumor response in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Materials and Methods This HIPAA-compliant retrospective, single-institution analysis was approved by the institutional review board, with waiver of informed consent. It included 79 patients with unresectable HCC who were treated with TACE. Baseline arterial phase contrast material-enhanced (CE) MR imaging was used to measure the overall and enhancing tumor diameters. A segmentation-based three-dimensional quantification of the overall and enhancing tumor volumes was performed in each patient. Numeric cutoff values (5 cm for diameters and 65 cm(3) for volumes) were used to stratify the patient cohort in two groups. Tumor response rates according to Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) guidelines were recorded for all groups. Survival was evaluated by using Kaplan-Meier analysis and was compared by using Cox proportional hazard ratios (HRs) after univariate and multivariate analysis. Results Stratification according to overall and enhancing tumor diameters did not result in a significant separation of survival curves (HR, 1.4; 95% confidence interval [CI]: 0.7, 2.5; P = .234; and HR, 1.6; 95% CI: 0.9, 2.8; P = .08, respectively). The stratification according to overall and enhancing tumor volume achieved significance (HR, 1.8; 95% CI: 0.9, 3.4; P = .022; and HR, 1.8; 95% CI: 1.1, 3.1; P = .017, respectively). As for tumor response, higher response rates were observed in smaller lesions compared with larger lesions, when the 5-cm threshold (27% vs 15% for mRECIST and 45% vs 24% for EASL) was used. Conclusion As opposed to anatomic tumor diameter as the most commonly used staging marker, volumetric assessment of lesion size and enhancement on baseline CE MR images is strongly associated with survival of patients with HCC who were treated with TACE.

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Comparison of three dimensional synergistic analyses of percentage versus logarithmic data in antiviral studies.

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Comparison of three dimensional synergistic analyses of percentage versus logarithmic data in antiviral studies.

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