Leptin receptor-expressing cells in the ventromedial nucleus of the hypothalamus contribute to enhanced CCK-induced satiety following central leptin injection.

Others have shown that leptin and cholecystokinin (CCK) act synergistically to suppress food intake. Experiments described here tested whether leptin in the ventromedial hypothalamus (VMH) contributes to the synergy with peripheral CCK in male Sprague Dawley rats. A subthreshold injection of 50-ng leptin into the VMH 1 h before a peripheral injection of 1 µg/kg CCK did not change the response to CCK in rats offered chow or low-fat purified diet, but did exaggerate the reduction in intake of high-fat diet 30 min and 1 h after injection in rats that had been food deprived for 8 h. By contrast, deletion of leptin receptor-expressing cells in the VMH using leptin-conjugated saporin (Lep-Sap) abolished the response to peripheral CCK in chow-fed rats. Lateral ventricle injection of 2-µg leptin combined with peripheral CCK exaggerated the inhibition of chow intake for up to 6 h in control rats treated with Blank-saporin, but not in Lep-Sap rats. Blank-Saporin rats offered low- or high-fat purified diet also demonstrated a dose-response inhibition of intake that reached significance with 1 µg/kg of CCK for both diets. CCK did not inhibit intake of Lep-Sap rats in either low- or high-fat-fed rats. Thus, although basal activation of VMH leptin receptors makes a significant contribution to the synergy with CCK, increased leptin activity in the VMH does not exaggerate the response to CCK in intact rats offered low-fat diets, but does enhance the response in those offered high-fat diet.NEW & NOTEWORTHY Leptin is a feedback signal in the control of energy balance, whereas cholecystokinin (CCK) is a short-term satiety signal that inhibits meal size. The two hormones synergize to promote satiety. We tested whether leptin receptors in the ventromedial nucleus of the hypothalamus (VMH) contribute to the synergy. The results suggest that there is a requirement for a baseline level of activation of leptin receptors in the VMH in order for CCK to promote satiety.

Effect of intraoperative methadone vs other opioids on postoperative outcomes: a meta-analysis of randomized controlled studies.

ABSTRACT: Recent randomized controlled trials comparing the efficacy between intraoperative methadone and other opioids on postoperative outcomes have been limited by their small sample sizes and conflicting results. We performed a meta-analysis on randomized controlled trials which investigated outcomes between methadone and an opioid control group. Primary outcome data included postoperative opioid consumption, number of patients who received postoperative opioids, time to first analgesic, and pain scores. Secondary outcomes included time to extubation and incidence of nausea, vomiting, and respiratory depression. Statistical analysis was performed using RevMan. A P < 0.05 was considered statistically significant. Nine studies comprising 632 patients were included. There was no statistically significant reduction in opioid consumption postoperatively between the groups. Forty-seven percentage of patients in the methadone group received a dose of opioid postoperatively compared with 55% in the other opioids control group, which was not statistically significant. (P = 0.25) There was no difference in average time to receiving first postoperative analgesic among the groups. Pain scores within 24 hours were significantly lower in the methadone group when compared with other opioids (8 studies, n = 622, -0.49 [-0.74, -0.23], P = 0.002). However, there was no difference between 24 and 72 hours. There was no difference among the groups with respect to extubation time, nausea, vomiting, or respiratory depression. This meta-analysis concludes that there is currently insufficient evidence for the use of intraoperative methadone, when compared with other opioids. Although there was a decrease in average pain scores with methadone when compared with controls at 24 hours, there was no difference between 24 and 72 hours.

Per- and polyfluoroalkyl substances in sera from children 3 to 11 years of age participating in the National Health and Nutrition Examination Survey 2013-2014.

Several per- and polyfluoroalkyl substances (PFAS) have been measured in U.S. National Health and Nutrition Examination Survey (NHANES) participants 12 years of age and older since 1999-2000, but PFAS data using NHANES individual samples among children younger than 12 years do not exist. To obtain the first nationally representative PFAS exposure data in U.S. children, we quantified serum concentrations of 14 PFAS including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), in a nationally representative subsample of 639 3-11year old participants in NHANES 2013-2014. We used on-line solid-phase extraction coupled to isotope dilution-high performance liquid chromatography-tandem mass spectrometry; limits of detection were 0.1ng/mL for all analytes. We calculated geometric mean concentrations, determined weighted Pearson correlations, and used linear regression to evaluate associations of sex, age (3-5 vs 6-11 years), race/ethnicity (Hispanic vs non-Hispanic), household income, and body mass index with concentrations of PFAS detected in more than 60% of participants. We detected PFOS, PFOA, PFHxS, and PFNA in all children at concentrations similar to those of NHANES 2013-2014 adolescents and adults, suggesting prevalent exposure to these PFAS or their precursors among U.S. 3-11year old children, most of whom were born after the phase out of PFOS in the United States in 2002. PFAS concentration differences by sex, race/ethnicity, and age suggest lifestyle differences that may impact exposure, and highlight the importance of identifying exposure sources and of studying the environmental fate and transport of PFAS.