Comparison of gallium-67 versus indium-111 monoclonal antibody (96.5, ZME-018) in detection of human melanoma in athymic mice

We compared the biodistribution of two radiolabeled, whole, tumor selective monoclonal antibodies [( 111In]96.5, [111In]ZME-018) to 67Ga in nude mice bearing a human melanoma known to express p97 antigen. Localization of gallium was determined 48 hr following i.v. injection. Localization of the radiolabeled antibodies was determined at 3 days and 7 days following i.v. injection. All agents showed more or less similar absolute tumor uptake which varied between 22% and 36% of the injected dose per gram of tumor. Only the tumor uptake of [111In]96.5 antibody at 7 days was significantly lower than the 67Ga uptake at 48 hr. However, uptake in normal tissues was generally higher for both antibodies at 3 and 7 days than for 67Ga uptake at 48 hr. Therefore, the tumor-to-blood ratio for 67Ga was tenfold higher than that for either antibody, the tumor-to-muscle ratio was twofold higher. Bone was the only organ in which the tumor-to-organ ratio was consistently higher with radiolabeled antibody than with 67Ga. The tumor-to-liver and tumor-to-intestine ratios were comparable. Localization of the two tumor selective antibodies was greater than a nonspecific "control antibody" [( 111In]CEA) and change in specific activity from 0.17 mCi/mg to 3.3 mCi/mg did not influence localization. From these animal data it may be anticipated that tumor imaging with [111In]96.5 or [111In]ZME-018 will not be superior to imaging with 67Ga for detection of melanoma.     

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo^®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo^® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo^®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo^® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.     

Effect of postbariatric maternal weight loss and surgery to conception interval on perinatal outcomes of nulliparous women

BackgroundBariatric surgery is associated with an increased risk of delivering a small neonate. The role of maternal weight loss and surgery to conception interval is unclear.ObjectivesTo investigate the effect of maternal weight loss, as a result of bariatric surgery, and surgery to conception interval on fetal growth and birthweight (BW).SettingInner London Teaching HospitalMethodsWe studied prospectively nulliparous women with previous bariatric surgery. Information on type, time, and presurgery weight was obtained. Surgery-to-conception interval was calculated as the time between surgery and conception, defined as the fourteenth day of the pregnancy dated by first trimester ultrasound scan. In the first trimester, maternal weight was measured. Assessment of maternal weight change between presurgery and first trimester of pregnancy was defined as total weight loss (TWL) (%). Fetal ultrasound scans were performed twice; 30–32 and 35–37 weeks’ gestation and estimated fetal weight (EFW) was calculated. Fetal growth rate was calculated as the ratio of EFW increase (in grams) between 30–32 and 35–37 weeks divided by the time interval (in days) between the 2 examinations. BW was recorded.ResultsThe study included 54 pregnant women, 26 with a restrictive procedure (gastric band or vertical sleeve gastrectomy) and 28 with a gastric bypass. Surgery to conception interval was not a significant predictor of the offspring’s growth. Maternal TWL was a significant predictor of fetal growth rate (P = .04) and predictor of BW (P = .005), even after adjustment for confounders.ConclusionsMaternal weight loss, as a result of bariatric surgery, has an inverse correlation with fetal growth rate and BW.     

Frontotemporal Regulation of Subjective Value to Suppress Impulsivity in Intertemporal Choices

Impulsive decisions arise from preferring smaller but sooner rewards compared with larger but later rewards. How neural activity and attention to choice alternatives contribute to reward decisions during temporal discounting is not clear. Here we probed (1) attention to and (2) neural representation of delay and reward information in humans (both sexes) engaged in choices. We studied behavioral and frequency-specific dynamics supporting impulsive decisions on a fine-grained temporal scale using eye tracking and MEG recordings. In one condition, participants had to decide for themselves but pretended to decide for their best friend in a second prosocial condition, which required perspective taking. Hence, conditions varied in the value for themselves versus that pretending to choose for another person. Stronger impulsivity was reliably found across three independent groups for prosocial decisions. Eye tracking revealed a systematic shift of attention from the delay to the reward information and differences in eye tracking between conditions predicted differences in discounting. High-frequency activity (175-250 Hz) distributed over right frontotemporal sensors correlated with delay and reward information in consecutive temporal intervals for high value decisions for oneself but not the friend. Collectively, the results imply that the high-frequency activity recorded over frontotemporal MEG sensors plays a critical role in choice option integration.SIGNIFICANCE STATEMENT Humans face decisions between sooner smaller rewards and larger later rewards daily. An objective benefit of losing weight over a longer time might be devalued in face of ice cream because they prefer currently available options because of insufficiently considering long-term alternatives. The degree of contribution of neural representation and attention to choice alternatives is not clear. We investigated correlates of such decisions in participants deciding for themselves or pretending to choose for a friend. Behaviorally participants discounted less in self-choices compared with the prosocial condition. Eye movement and MEG recordings revealed how participants represent choice options most evident for options with high subjective value. These results advance our understanding of neural mechanisms underlying decision-making in humans.