Colorants in Cheese Manufacture: Production, Chemistry, Interactions, and Regulation

Colored Cheddar cheeses are prepared by adding an aqueous annatto extract (norbixin) to cheese milk; however, a considerable proportion (∼20%) of such colorant is transferred to whey, which can limit the end use applications of whey products. Different geographical regions have adopted various strategies for handling whey derived from colored cheeses production. For example, in the United States, whey products are treated with oxidizing agents such as hydrogen peroxide and benzoyl peroxide to obtain white and colorless spray‐dried products; however, chemical bleaching of whey is prohibited in Europe and China. Fundamental studies have focused on understanding the interactions between colorants molecules and various components of cheese. In addition, the selective delivery of colorants to the cheese curd through approaches such as encapsulated norbixin and microcapsules of bixin or use of alternative colorants, including fat‐soluble/emulsified versions of annatto or beta‐carotene, has been studied. This review provides a critical analysis of pertinent scientific and patent literature pertaining to colorant delivery in cheese and various types of colorant products on the market for cheese manufacture, and also considers interactions between colorant molecules and cheese components; various strategies for elimination of color transfer to whey during cheese manufacture are also discussed

The application of precision dosing in the use of sertraline throughout pregnancy for poor and ultra-rapid metaboliser CYP 2C19 subjects: a virtual clinical trial pharmacokinetics study:A virtual clinical trial pharmacokinetics study

Sertraline is known to undergo changes in pharmacokinetics during pregnancy. CYP 2C19 has been implicated in the interindividual variation in clinical effect associated with sertraline activity. However, knowledge of suitable dose titrations during pregnancy and within CYP 2C19 phenotypes is lacking. A pharmacokinetic modeling virtual clinical trials approach was implemented to: (i) assess gestational changes in sertraline trough plasma concentrations for CYP 2C19 phenotypes, and (ii) identify appropriate dose titration strategies to stabilize sertraline levels within a defined therapeutic range throughout gestation. Sertraline trough plasma concentrations decreased throughout gestation, with maternal volume expansion and reduction in plasma albumin being identified as possible causative reasons. All CYP 2C19 phenotypes required a dose increase throughout gestation. For extensive metabolizer (EM) and ultrarapid metabolizer (UM) phenotypes, doses of 100–150 mg daily are required throughout gestation. For poor metabolizers (PM), 50 mg daily during trimester 1 followed by a dose of 100 mg daily in trimesters 2 and 3 are required

Salmonella Enteritidis Infections, United States, 1985–1999

Salmonella enterica serotype Enteritidis emerged as an important illness during the 1980s. Investigations showed that consumption of undercooked eggs was the major risk factor for disease, and a variety of prevention and control efforts were initiated during the 1990s. We describe sporadic infections and outbreaks of S. Enteritidis in the United States from 1985 through 1999 and discuss prevention and control efforts. After reaching a high of 3.9 per 100,000 population in 1995, S. Enteritidis infections declined to 1.98 per 100,000 in 1999. While the total number of outbreaks decreased by half, those in the western states tripled. Outbreaks of S. Enteritidis phage type 4 infections accounted for 49% of outbreaks in 1999. Outbreak-associated deaths in health facilities decreased from 14 in 1987 to 0 in 1999. Overall, rates of sporadic S. Enteritidis infection, outbreaks, and deaths have declined dramatically. For further reductions, control measures should continue to be applied along the entire farm-to-table continuum

Biomarkers of Exposure: A Case Study with Inorganic Arsenic

The environmental contaminant inorganic arsenic (iAs) is a human toxicant and carcinogen. Most mammals metabolize iAs by reducing it to trivalency, followed by oxidative methylation to pentavalency. iAs and its methylated metabolites are primarily excreted in urine within 4–5 days by most species and have a relatively low rate of bioaccumulation. Intra- and interindividual differences in the methylation of iAs may affect the adverse health effects of arsenic. Both inorganic and organic trivalent arsenicals are more potent toxicants than pentavalent forms. Several mechanisms of action have been proposed for arsenic-induced toxicity, but a scientific consensus has not been achieved. Biomarkers of exposure may be used to quantify exposure to iAs. The most common biomarker of exposure for iAs is the measurement of total urinary arsenic. However, consumption of seafood containing high concentrations of organic arsenic can confound estimation of iAs exposure. Because these organic species are thought to be relatively nontoxic, their presence in urine may not represent increased risk. Speciation of urinary arsenic into inorganic and organic forms, and even oxidation state, gives a more definitive indication of the exposure to iAs. Questions still remain, however, as to how reliably the measurement of urinary arsenic, either total or speciated, may predict arsenic concentrations at target tissues as well as how this measurement could be used to assess chronic exposures to iAs

How do multi-stage, multi-arm trials compare to the traditional two-arm parallel group design – a reanalysis of 4 trials

<p>Abstract</p> <p>Background</p> <p>To speed up the evaluation of new therapies, the multi-arm, multi-stage trial design was suggested previously by the authors.</p> <p>Methods</p> <p>In this paper, we evaluate the performance of the two-stage, multi-arm design using four cancer trials conducted at the MRC CTU. The performance of the design at fictitious interim analyses is assessed using a conditional bootstrap approach.</p> <p>Results</p> <p>Two main aims are addressed: the error rate of correctly carrying on/stopping the trial at an interim analysis as well as quantifying the gains in terms of resources by employing this design. Furthermore, we make suggestions for the best timing of this interim analysis.</p> <p>Conclusion</p> <p>Multi-arm, multi-stage trials are an effective way of speeding up the therapy evaluation process. The design performs well in terms of the type I and II error rates.</p

A pilot study to evaluate the application of a generic protein standard panel for quality control of biomarker detection technologies

<p>Abstract</p> <p>Background</p> <p>Protein biomarker studies are currently hampered by a lack of measurement standards to demonstrate quality, reliability and comparability across multiple assay platforms. This is especially pertinent for immunoassays where multiple formats for detecting target analytes are commonly used.</p> <p>Findings</p> <p>In this pilot study a generic panel of six non-human protein standards (50 - 10^7 pg/mL) of varying abundance was prepared as a quality control (QC) material. Simulated "normal" and "diseased" panels of proteins were prepared in pooled human plasma and incorporated into immunoassays using the Meso Scale Discovery^®(MSD^®) platform to illustrate reliable detection of the component proteins. The protein panel was also evaluated as a spike-in material for a model immunoassay involving detection of ovarian cancer biomarkers within individual human plasma samples. Our selected platform could discriminate between two panels of the proteins exhibiting small differences in abundance. Across distinct experiments, all component proteins exhibited reproducible signal outputs in pooled human plasma. When individual donor samples were used, half the proteins produced signals independent of matrix effects. These proteins may serve as a generic indicator of platform reliability.</p> <p>Each of the remaining proteins exhibit differential signals across the distinct samples, indicative of sample matrix effects, with the three proteins following the same trend. This subset of proteins may be useful for characterising the degree of matrix effects associated with the sample which may impact on the reliability of quantifying target diagnostic biomarkers.</p> <p>Conclusions</p> <p>We have demonstrated the potential utility of this panel of standards to act as a generic QC tool for evaluating the reproducibility of the platform for protein biomarker detection independent of serum matrix effects.</p

Elucidation of the controlled-release behavior of metoprolol succinate from directly compressed xanthan gum-chitosan polymers: computational and experimental studies

The development and evaluation of a controlled-release (CR) pharmaceutical solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS) and metoprolol succinate (MS) is reported. The research is, partly, based upon the utilization of computational tools; in this case molecular dynamics simulations (MDs) and response surface method (RSM), in order to underpin the design/prediction and to minimize the experimental work required to achieve the desired pharmaceutical outcomes. The capability of the system to control the release of MS was studied as a function of LCS (% w/w) and total polymer (LCS and XG) to drug ratio (P:D) at different tablet tensile strengths. MDs trajectories, obtained by using different ratios of XG:LCS as well as XG and high molecular weight CS (HCS), showed that the driving force for the interaction between XG and LCS is electrostatic in nature, the most favourable complex is formed when LCS is used at 15 % (w/w) and, importantly, that the interaction between XG and LCS is more favourable than that between XG and HCS. RSM outputs revealed that the release of the drug from the LCS/XG matrix is highly dependent on both the % LCS and the P:D ratio and that the required CR effect can be achieved when using weight fractions of LCS ≤ 20% and P:D ratios ≥ 2.6:1. Results obtained from in-vitro drug release and swelling studies on the prepared tablets showed that using LCS at the weight fractions suggested by MDs and RSM data plays a major role in overcoming the high sensitivity of the controlled drug release effect of XG on ionic strength and pH changes of the dissolution media. In addition, it was found that polymer relaxation is the major contributor to the release of MS from LCS-XG tablets. Using Raman spectroscopy, MS was shown to be localized more in the core of the tablets at the initial stages of dissolution due to film formation between LCS and XG on the tablet surface which prevents excess water penetration into the matrix. In the later stages of the dissolution process, the film starts to dissolve/erode allowing full tablet hydration and a uniform drug distribution in the swollen tablet

Dosing and Monitoring of Trace Elements in Long‐Term Home Parenteral Nutrition Patients

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141314/1/jpen0736.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141314/2/jpen0736-sup-0001.pd