NC100668, A NEW TRACER FOR IMAGING OF VENOUS THROMBOEMBOLISM: DISPOSITION AND METABOLISM IN RATS

ABSTRACT: The NC100668 consists of a 13-amino acid peptide, N-terminally blocked with an acetyl group containing an iodinated tyrosine and coupled to a Tc-chelator (NC100194) via the C-terminal glycine. Using the common three-letter abbreviations for amino acids, the structure of NC100668 is Acetyl-Asn-Gln-Glu-Gln-Val-Ser-ProTyr(3-iodo)-Thr-Leu-Leu-Lys-Gly-NC100194, where NC100194 is represented by the chemical formula -NH-CH 2 -CH 2 -N(CH 2 -CH 2 -NH-C(CH 3 ) 2 -C(CH 3 )ϭN-OH) 2 . The detailed structure is shown in 99m Tc-NC100668 is being developed as a diagnostic radiopharmaceutical for imaging of venous thromboembolism, which is a major health problem with an estimated average annual incidence in the United States exceeding 1 per 1000 Diagnostic radiopharmaceuticals are radioactive substances that are administered to patients. Many of these agents are labeled with the ␥-emitter 99m Tc, which has a half-life of 6.02 h doi:10.1124/dmd.105.006239. ABBREVIATIONS: NC100668, Acetyl-Asn-Gln-Glu-Gln-Val-Ser-Pro-Tyr(3-iodo)-Thr-Leu-Leu-Lys-Gly-NC100194; NC100194, -NH-CH 2 -CH 2 -N(CH 2 -CH 2 -NH-C(CH 3 ) 2 -C(CH 3 )ϭN-OH) 2 ; Fmoc, 9-fluorenyloxycarbonyl; Boc, butyl oxy carbonyl; PyBOP, benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate; DMF, dimethylformamide; TFA, trifluoroacetic acid; MS, mass spectrometry; HPLC, high-performance liquid chromatography; QWBA, quantitative whole-body autoradiography; SAC, self-absorption coefficient; % ID, percentage of injected dose; LC-MS, liquid chromatography-mass spectrometry; MS/MS, tandem mass spectrometry

Evaluation of energy and dietary intake estimates from a food frequency questionnaire using independent energy expenditure measurement and weighed food records

<p>Abstract</p> <p>Background</p> <p>We have developed a food frequency questionnaire (FFQ) for the assessment of habitual diet, with special focus on the intake of fruit, vegetables and other antioxidant-rich foods and beverages. The aim of the present study was to evaluate the relative validity of the intakes of energy, food and nutrients from the FFQ.</p> <p>Methods</p> <p>Energy intake was evaluated against independent measures of energy expenditure using the ActiReg^®system (motion detection), whereas 7-days weighed food records were used to study the relative validity of food and nutrient intake. The relationship between methods was investigated using correlation analyses and cross-classification of participants. The visual agreement between the methods was evaluated using Bland-Altman plots.</p> <p>Results</p> <p>We observed that the FFQ underestimated the energy intake by approximately 11% compared to the energy expenditure measured by the ActiReg^®. The correlation coefficient between energy intake and energy expenditure was 0.54 and 32% of the participants were defined as under-reporters. Compared to the weighed food records the percentages of energy from fat and added sugar from the FFQ were underestimated, whereas the percentage of energy from total carbohydrates and protein were slightly overestimated. The intake of foods rich in antioxidants did not vary significantly between the FFQ and weighed food records, with the exceptions of berries, coffee, tea and vegetables which were overestimated. Spearman's Rank Order Correlations between FFQ and weighed food records were 0.41 for berries, 0.58 for chocolate, 0.78 for coffee, 0.61 for fruit, 0.57 for fruit and berry juices, 0.40 for nuts, 0.74 for tea, 0.38 for vegetables and 0.70 for the intake of wine.</p> <p>Conclusions</p> <p>Our new FFQ provides a good estimate of the average energy intake and it obtains valid data on average intake of most antioxidant-rich foods and beverages. Our study also showed that the FFQs ability to rank participants according to intake of total antioxidants and most of the antioxidant-rich foods was good.</p

Disease eradication and the challenges of global resource mobilization. An experimental approach to understand the perception of the benefits of polio eradication

The global effort to eradicate polio began in 1988. The target of the effort was to eradicate the disease by the year 2000, a target which was not attained. The annual number of polio cases has been reduced from 350,000 in 1988, to 650 in 2011. Research shows that financial setbacks are the main reason why polio has not yet been eradicated. When donor countries contribute less than the needed amount to eradicate, they signal that this effort is not in their interest. Cost-benefit analysis demonstrates that the high short term costs involved in the eradication effort are outweighed by the long term benefits of not needing to vaccinate the population. So why has polio not been eradicated? Studies show that even though a country would benefit from increasing its contribution, it will not do so unless other countries do the same. Using an experimental approach we have investigated how the level of contributions differs under two conditions: if contributions are made on behalf of one donor country or on behalf of the whole group of donor countries. We have also tested to see if information emphasizing the benefits of eradication will increase contributions. The results show a weak difference between contributions made when playing the role as the policy maker for a country compared to contributions made when playing the same role for the whole group. Information did not have an effect on the performance. The experimental group was made up of students playing the role of policy makers. The make-up of the experimental group may have affected the results of the experiment. Students may have a better understanding of long term benefits and base their decisions on different incentives than policy makers, resulting in the weak difference of treatments. However, there may also be misperceptions of long term benefits which need different corrections than written information can give