Fat Emulsion(C14-24)

Intralipid^® is widely used as a tissue-mimicking phantom due to its optical similarity to biological tissues, i.e., high scattering and low absorption of light. Accurate modeling of the optical behavior of phantoms requires detailed knowledge of the properties of its scatterers.

We aim to determine the particle size distribution (PSD), concentration, and refractive index (RI) of particles in Intralipid^® 20%.

Cryo-electron microscopy, three different flow cytometers, and microfluidic resistive pulse sensing were used to measure the size distribution and concentration of particles in Intralipid^® 20%. To select the most accurate technique, the measured volume fraction of lipid particles was calculated and compared with the expected volume fraction (0.227). The measured size distribution and RI of soybean oil and Dulbecco's phosphate-buffered saline were used to calculate key optical parameters for the independent, single scattering regime. Calculations were performed with Mie theory across the 400- to 700-nm-wavelength range. Analytical expressions were then fitted to describe the wavelength dependence of each optical parameter.

The PSD, obtained from measurements of more than 10 million particles, spanned from 67 nm to over 2000 nm, with concentration decreasing continuously as diameter increased. The particle volume fraction calculated from the PSD deviated by less than 2% from the expected value, confirming the accuracy of the measurements. Optical parameters calculated from the PSD and RIs, including the scattering coefficient, phase function, anisotropy factor, and reduced scattering coefficient, showed good agreement with values reported in the literature. These parameters were also well described by empirical fits ( __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__R > 0.97 ).

The accurate measurement of particle size, concentration, and RI of Intralipid^® 20% supports the use of Intralipid^® as a reliable tissue-mimicking phantom and calibration sample in optical studies.

Early-lactating dairy cows are vulnerable to metabolic dysfunctions and diseases and the consequent negative effects of these disturbances on appetite. The exaggerated response of early-lactating cows to metabolic disturbances is illustrated by their response to a hyperinsulinemic-euglycemic clamp (HEC) performed over a 48-h period. Initiation of HEC on d 7 of early lactation (EL) reduced feed intake by 33% but had no effect when performed in late pregnancy (LP, 31 d prepartum). We asked whether growth differentiation factor 15 (GDF15), a novel hormone inhibiting feed intake via activation of neuronal centers, could explain the effect of HEC on appetite in EL. This focus was prompted by increased GDF15 production in primates and rodents experiencing metabolic stressors. In plasma samples collected immediately before and after a 48-h period of HEC in EL and LP, HEC increased plasma GDF15 exclusively in EL, and this increase was positively associated with the reduction in feed intake. The major site of GDF15 production in EL was identified as liver on the basis of 7.7- to 87-fold higher expression than adipose tissue or muscle and increased hepatic GDF15 mRNA abundance during HEC. The HEC stimulated hepatic expression of the GDF15 transcriptional activators ATF4 and CHOP across physiological states and expression of the indicator of amino acid deficiency ASNS in EL but not LP. We next asked whether plasma GDF15 is also regulated by a subset of metabolic disturbances prevailing in EL cows (elevated plasma fatty acids, excessive liver triglyceride, and ketosis). The effect of increased plasma fatty acids was evaluated by i.v. infusion of a lipid emulsion (intralipid) in nonpregnant, nonlactating cows in the absence or presence of glucagon treatment. Intralipid caused a progressive rise in plasma GDF15; this stimulatory effect was increased in the presence of glucagon, resulting in a 2.4-fold increase over control after 13 h of infusion. Positive effects of intralipid were associated with increased hepatic expression of GDF15 and its transcriptional activators ATF4 and sXBP1; presence of glucagon increased GDF15 mRNA further but had no additional effect on ATF4 or sXBP1. Indices of GDF15 production were examined in healthy cows segregated on d 7 of lactation as having low (<5.2%) and high (>11.5%) liver triglyceride; neither plasma GDF15 nor hepatic GDF15 mRNA differed between the 2 groups. Finally, plasma GDF15 was measured in early-lactating dairy cows remaining healthy or diagnosed with clinical ketosis. Plasma GDF15 was 1.8-fold higher in ketotic than healthy cows. Overall, these data show upregulation of GDF15 production by a subset of metabolic factors and raise the possibility that GDF15 could contribute to the lower appetitive drive of early-lactating cows experiencing metabolic disturbances.