Comparative analyses of single-nucleotide polymorphisms in the TNF promoter region provide further validation for the vervet monkey model of obesity.

Tumor necrosis factor is a cytokine that plays critical roles in inflammation, the innate immune response, and a variety of other physiologic and pathophysiologic processes. In addition, TNF has recently been shown to mediate an intersection of chronic, low-grade inflammation and concurrent metabolic dysregulation associated with obesity and its comorbidities. As part of an ongoing initiative to further characterize vervet monkeys originating from St Kitts as an animal model of obesity and inflammation, we sequenced and genotyped the human ortholog vervet TNF gene and approximately 1 kb of the flanking 3' and 5' regions from 265 monkeys in a closed, pedigreed colony. This process revealed a total of 11 single-nucleotide polymorphisms (SNPs) and a single 4-bp insertion-deletion, with minor allele frequencies of 0.08 to 0.39. Many of these polymorphisms were in strong or complete linkage disequilibrium with each other, and all but 1 were contained within a single haplotype block, comprising 5 haplotypes with frequencies of 0.075 to 0.298. Using sequences from humans, chimpanzees, vervets, baboons, and rhesus macaques, phylogenetic shadowing of the TNF promoter region revealed that vervet SNPs, like the SNPs in related species, were clustered nonrandomly and nonuniformly around conserved transcription factor binding sites. These data, combined with previously defined heritable phenotypes, permit future association analyses in this nonhuman primate model and have great potential to help dissect the genetic and nongenetic contributions to complex diseases like obesity. More broadly, the sequence data and comparative analyses reported herein facilitates study of the evolution of regulatory sequences of inflammatory and immune-related genes.

[Performance limiting causes in single use unit systems for the measurement of PO2 and PCO2 in blood]. / Facteurs de limitation des performances des appareils a cassettes a usage unique pour la mesure de la PO2 et de la PCO2 du sang total.

Having had the opportunity of testing two of the three commercially available single use unit systems (i-STAT and OPTI-1), we have listed a series of performance limiting factors which they share, even though, their detectors being based on different methodologies, they have specific causes of dysfunction. PO2 detectors face the worse problems for different reasons. Temperature control is critical: the cassette or at last the detectors, the internal solution and the specimen have to be heated to 37 C, thermostabilisation to one tenth of degree centigrade is a must. Gas equilibration between liquid phases, the outside ambiance and the plastic material can raise problems: a decrease of the external barometric pressure alters the result, an absence of oxygen buffer capacity can induce modifications of the PO2 in the solutions. The transition of the detectors from a dry to a wet stage can provoke changes of the final result in case of accidental pre-humidication of the cassette. The presence of a single internal solution generates problems linked to a single point calibrage procedure which is a source of variability. The general quality of the cassette can only be evaluated by numerous internal electronic checks: increasing the severity of the controls improves quality but increases the number of rejected cassettes. External quality control through classical procedures are not applicable and finally the quality of the cassettes depends primarily on rigorous manufacturing conditions.

[Analytical performances of the i-STAT portable clinical analyzer for the measurement of PO2 and PCO2]. / Evaluation des performances analytiques du i-STAT portable clinical analyzer pour la détermination des pressions partielles d'oxygène et de gaz carbonique dans le sang total.

Aware of some limitations on blood gas results, we performed an extensive evaluation before introducing i-STATs in our hospitals. Three i-STATs were tested in parallel with an ABL-520, on three types of cartridges (EG7, EG6 and EG3), using tonometered whole blood (9 gas levels, n = 720) and aqueous QC solutions (3 levels, n = 600). Reference systems were the theoretical calculated values from gas composition used for tonometry and results given by the ABL-520, respectively. On aqueous controls dispersion intervals reached 10-20 mmHg for both analytes for inter-lot as well as intra-lot data. PO2 values on blood showed marked dispersion: 5 mmHg (CV = 2 to 7%) at clinically critical levels. PCO2 showed several (10%) major outliers: mV recording of the PCO2 electrode allowed to incriminate a pre-humidification problem (due to incorrect shipping conditions). Once outliers have been discarted, there still was a 5 mmHg non negligible residual dispersion (CV = 3 to 5%). i-STAT analytical performances for blood gases which are the analytes whose determination at the bed-side is potentially the most useful, do not match capabilities of classical laboratory instruments. Thus even though the i-STAT approach represents a seducive solution for the STAT problem, for the moment, it's use cannot be recommended in a hospital environment where classical instruments can be made available.