Role of mouse CYP2E1 in the O-hydroxylation of p-nitrophenol: comparison of activities in hepatic microsomes from Cyp2e1(-/-) and wild-type mice.

Enzymatic activities are routinely used to identify the contribution of individual forms of cytochrome P450 in a particular biotransformation. p-Nitrophenol O-hydroxylation (PNPH) has been widely used as a measure of CYP2E1 catalytic activity. However, rat and human forms of CYP3A have also been shown to catalyze this activity. In mice, the contributions of CYP3A and CYP2E1 to PNPH activity are not known. Here we used hepatic microsomes from Cyp2e1(-/-) and wild-type mice to investigate the contributions of constitutively expressed and alcohol-induced murine CYP2E1 and CYP3A to PNPH activity. In liver microsomes from untreated mice, PNPH activity was much greater in wild-type mice compared with Cyp2e1(-/-) mice, suggesting a major role for CYP2E1 in catalyzing PNPH activity. Hepatic PNPH activities were not significantly different in microsomes from male and female mice, although the microsomes from females have dramatically higher levels of CYP3A. Treatment with a combination of ethanol and isopentanol resulted in induction of CYP3A proteins in wild-type and Cyp2e1(-/-) mice, as well as CYP2E1 protein in wild-type mice. The alcohol treatment increased PNPH activities in hepatic microsomes from wild-type mice but not from Cyp2e1(-/-) mice. Our findings suggest that in untreated and alcohol-treated mice, PNPH activity may be used as a specific probe for CYP2E1 and that constitutively expressed and alcohol-induced forms of mouse CYP3A have little to no role in catalyzing PNPH activity.     

Insulin resistance: a risk marker for disease and disability in the older person

Clinical metabolic studies have demonstrated that insulin action declines progressively with age in humans. In addition to its close association with Type 2 diabetes, which reduces life expectancy in older people, age‐related insulin resistance is implicated in pathogenesis of several highly prevalent disorders for which ageing is a major risk factor. These include atherosclerotic cardiovascular disease, dementia, frailty and cancer. Accordingly, insulin resistance may be viewed as biomarker of age‐related ill health and reduced lifespan. The rapidly rising number of older people, coupled with a high prevalence of insulin resistance resulting from obesity and sedentary lifestyles, presents unprecedented public health and societal challenges. Studies of centenarians have shown that preserved whole‐body sensitivity to insulin is associated with longevity. The mechanisms through which insulin action is associated with age‐related diseases remain unclear. Changes in body composition, i.e. sarcopenia and excess adiposity, may be more potent than age per se. Moreover, the impact of insulin resistance has been difficult to disentangle from the clustering of vascular risk factors that co‐segregate with the insulin resistance–hyperinsulinaemia complex. Potentially modifiable mediators of age‐related changes in insulin sensitivity include alterations in adipocytokines, impaired skeletal myocyte mitochondrial function and brown fat activity. The hypothesis that improving or maintaining insulin sensitivity preserves health and extends lifespan merits further evaluation. Practical non‐pharmacological interventions directed against age‐related insulin resistance remain underdeveloped. Novel metabolically active pharmacological agents with theoretical implications for some age‐related disorders are entering clinical trials. However, recent adverse experiences with the thiazolidinediones suggest the need for a cautious approach to the use of insulin sensitizing drugs in older people. This could be particularly important in the absence of diabetes where the risk to benefit analysis may be less favourable.     

Spectral Shift Originating from Non-linear Ultrasonic Wave Propagation and Its Effect on Imaging Resolution

An amplitude-dependent downshift in the fundamental wave spectrum of a propagating ultrasonic pulse caused by non-linear wave propagation is described. The effects of non-linearity and the associated downshift on spatial resolution are also studied. The amounts of downshift and spatial resolution are extracted from the numerically simulated beam profile based on the KZK equation. Results for a 25-MHz transducer reveal that non-linear effects can lead to 58% additional downshift in the centre frequency of a pulse compared with a linear case with downshift caused only by attenuation. This additional downshift causes about 50% degradation in axial resolution. However, as the beam becomes narrower from the non-linear effects, the overall effect of non-linearity still leads to improved lateral resolution (≤26%). Therefore, as non-linearity increases with wave pressure, it is concluded that the increase in source pressure improves lateral resolution and degrades axial resolution.     

Sociodemographic Differences in the Comprehension of Nutritional Labels on Food Products

ObjectiveTo examine comprehension of nutrition labels across sociodemographic groups using a measure of health literacy.MethodsCross-sectional survey of a community sample of adults including an adapted version of the Newest Vital Sign for Canadian Nutrition Facts table on prepackaged grocery products, including numerical conversion questions for calorie content and percent daily value.ResultsApproximately two thirds of participants were able to correctly identify calorie content and percent daily value from the nutrition label. Participants with higher education and higher income, those aged ≤ 64 years, and those who look at nutritional facts or calories were significantly more likely to estimate the correct calorie content. Participants were significantly more likely to correctly identify percent daily value if they reported higher education, higher income, and white ethnicity.Conclusions and ImplicationsApproximately one third of participants could not comprehend basic information on Canadian nutrition labels. Lower socioeconomic status was associated with poorer performance.     

The Significance of Calcified Fibrocartilage on the Cortical Endplate of the Translational Sheep Spine Model

To gain an understanding of the vertebral cortical endplate and factors that may affect the ability to achieve skeletal attachment to intervertebral implants and fusion, this study aimed to characterize the hypermineralized tissue on the cortical endplate of the vertebral body on a commonly used animal model. Skeletally mature sheep were injected with tetracycline prior to euthanasia and the C2‐C3, T5‐T6, and L2‐L3 spinal motion segments were excised and prepared. Vertebral tissues were imaged using backscatter electron (BSE) imaging, histology, and tetracycline labeling was used to assess bone remodeling within different tissue layers. It was determined that the hypermineralized tissue layer was calcified fibrocartilage (CFC). No tetracycline labels were identified in the CFC layer, in contrast to single and double labels that were present in the underlying bone, indicating the CFC present on the cortical endplate was not being actively remodeled. The average thickness of the CFC layer was 146.3 ± 70.53 µm in the cervical region, 98.2 ± 40.29 µm in the thoracic region, and 150.89 ± 69.25 µm in the lumbar region. This difference in thickness may be attributed to the regional biomechanical properties of the spine. Results from this investigation indicate the presence of a nonremodeling tissue on the cortical endplate of the vertebral body in sheep spines, which attaches the intervertebral disc to the vertebrae. This tissue, if not removed, would likely prevent successful bony attachment to an intervertebral device in spinal fusion studies and total disc replacement surgeries. Anat Rec, 296:736–744, 2013. © 2013 Wiley Periodicals, Inc.