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Obesity and type 2 diabetes are growing problems worldwide in adults and children. In this study, we focused on understanding the patterning of insulin resistance as a result of altered perinatal nutrition. We analyzed mice in which the binding site for PPAR[gamma] was deleted from the promoter of the cytosolic phosphoenolpyruvate carboxykinase gene (Pck1) ([PPARE.sup.-/-]). We analyzed pups from dams with the same genotype as well as fostered and cross-fostered pups. Pck1 expression and triglyceride concentration in the milk were measured. The PPARE mutation reduced Pck1 expression in white adipose tissue (WAT) to 2.2% of wild type (WT) and reduced Pck1 expression in whole mammary gland tissue to 1% of WT. The female [PPARE.sup.-/-] mice had reduced lipid storage in mammary gland adipocytes and in WAT, resulting in a 40% reduction of milk triglycerides during lactation. Pups from [PPARE.sup.-/-] dams had insulin resistance as early as 14 d after birth, a condition that persisted into adulthood. WT pups fostered by [PPARE.sup.-/-] dams had lower body weights and plasma insulin concentrations compared with WT pups reared by WT dams. [PPARE.sup.-/-] pups fostered by WT dams had improved glucose clearance compared with pups raised by [PPARE.sup.-/-] dams. [PPARE.sup.+/-] and [PPARE.sup.-/-] dams also patterned newborn pups for reduced growth and insulin resistance in utero. Thus, the in utero environment and altered nutrition during the perinatal period cause epigenetic changes that persist into adulthood and contribute to the development of insulin resistance. J. Nutr. 139: 2257-2265, 2009. Manuscript received July 21, 2009. Initial review completed August 3, 2009. Revision accepted September 17, 2009. First published online October 7, 2009; doi: 10.3945/jn.109.113092.

Autosomal recessive polycystic kidney disease (ARPKD) is a potentially lethal multi-organ disease affecting both the kidneys and the liver. Unfortunately, there are currently no non-invasive methods to monitor liver disease progression in ARPKD patients, limiting the study of potential therapeutic interventions. Herein, we perform an initial investigation of T1 relaxation time as a potential imaging biomarker to quantitatively assess the two primary pathologic hallmarks of ARPKD liver disease: biliary dilatation and periportal fibrosis in the PCK rat model of ARPKD. T1 relaxation time results were obtained for five PCK rats at 3 months of age using a Look-Locker acquisition on a Bruker BioSpec 7.0 T MRI scanner. Six three-month-old Sprague-Dawley (SD) rats were also scanned as controls. All animals were euthanized after the three-month scans for histological and biochemical assessments of bile duct dilatation and hepatic fibrosis for comparison. PCK rats exhibited significantly increased liver T1 values (mean ± standard deviation = 935 ± 39 ms) compared with age-matched SD control rats (847 ± 26 ms, p = 0.01). One PCK rat exhibited severe cholangitis (mean T1 = 1413 ms), which occurs periodically in ARPKD patients. The observed increase in the in vivo liver T1 relaxation time correlated significantly with three histological and biochemical indicators of biliary dilatation and fibrosis: bile duct area percent ( R = 0.85, p = 0.002), periportal fibrosis area percent ( R = 0.82, p = 0.004), and hydroxyproline content ( R = 0.76, p = 0.01). These results suggest that hepatic T1 relaxation time may provide a sensitive and non-invasive imaging biomarker to monitor ARPKD liver disease. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Obesity and type 2 diabetes are growing problems worldwide in adults and children. In this study, we focused on understanding the patterning of insulin resistance as a result of altered perinatal nutrition. We analyzed mice in which the binding site for PPARy was deleted from the promoter of the cytosolic phosphoenolpyruvate carboxykinase gene (Pck1)/PPARE-/-. We analyzed pups from dams with the same genotype as well as fostered and cross-fostered pups. Pckl expression and triglyceride concentration in the milk were measured. The PPARE mutation reduced Pckl expression in white adipose tissue (WATI to 2.2% of wild type (WT) and reduced Pckl expression in whole mammary gland tissue to 1% of WT. The female PPARE-/- mice had reduced lipid storage in mammary gland adipocytes and in WAT, resulting in a 40% reduction of milk triglycerides during lactation. Pups from PPARE-/- dams had insulin resistance as early as 14 d after birth, a condition that persisted into adulthood. WT pups fostered by PPARE-/- dams had lower body weights and plasma insulin concentrations compared with WT pups reared by WT dams. PPARE-/- pups fostered by WT dams had improved glucose clearance compared with pups raised by PPARE-/- dams. PPARE-/- and PPARE-/- dams also patterned newborn pups for reduced growth and insulin resistance in utero. Thus, the in utero environment and altered nutrition during the perinatal period cause epigenetic changes that persist into adulthood and contribute to the development of insulin resistance. [ABSTRACT FROM AUTHOR]

The Nuclear Regulatory Commission's Regulatory Guide 8.39, 'Release of Patients Administered Radioactive Materials,' permits licensees toauthorize the release of patients treated with 131I [(T1/2) p = 8.04 d] if the total dose equivalent to another individual from the released individual is not likely to exceed 5 millisieverts (0.5 rem). This paper guides the reader through the derivation of an easy-to-use formula that demonstrates how to calculate the total dose equivalent, using patient-specific parameters that an individual may receive from a patient who has been administered a therapeutic dose of 131I, as compared to the NRC's Reg. Guide 8.39 (see Appendix A). Patient-specific parameters include the individual thyroidal uptake, the patient's physical dimensions, attenuation of radiation by body tissues, buildup of secondary photons, whole body and thyroid retention functions as well as the distance and time the patient is around others. This paper also demonstrates how to calculate an inpatient's discharge time, so that the patient will not expose other individuals above the desired total dose equivalent set by the Radiation Safety Officer (RSO). [ABSTRACT FROM AUTHOR]

Autosomal recessive polycystic kidney disease (ARPKD) is a potentially lethal multi-organ disease affecting both the kidneys and the liver. Unfortunately, there are currently no non-invasive methods to monitor liver disease progression in ARPKD patients, limiting the study of potential therapeutic interventions. Herein, we perform an initial investigation of T1 relaxation time as a potential imaging biomarker to quantitatively assess the two primary pathologic hallmarks of ARPKD liver disease: biliary dilatation and periportal fibrosis in the PCK rat model of ARPKD. T1 relaxation time results were obtained for five PCK rats at 3 months of age using a Look-Locker acquisition on a Bruker BioSpec 7.0 T MRI scanner. Six three-month-old Sprague-Dawley (SD) rats were also scanned as controls. All animals were euthanized after the three-month scans for histological and biochemical assessments of bile duct dilatation and hepatic fibrosis for comparison. PCK rats exhibited significantly increased liver T1 values (mean ± standard deviation = 935 ± 39 ms) compared with age-matched SD control rats (847 ± 26 ms, p = 0.01). One PCK rat exhibited severe cholangitis (mean T1  = 1413 ms), which occurs periodically in ARPKD patients. The observed increase in the in vivo liver T1 relaxation time correlated significantly with three histological and biochemical indicators of biliary dilatation and fibrosis: bile duct area percent (R = 0.85, p = 0.002), periportal fibrosis area percent (R = 0.82, p = 0.004), and hydroxyproline content (R = 0.76, p = 0.01). These results suggest that hepatic T1 relaxation time may provide a sensitive and non-invasive imaging biomarker to monitor ARPKD liver disease., (Copyright © 2015 John Wiley & Sons, Ltd.)