Background and Purpose-The evaluation of the leptin:adiponectin ratio (L:A) has been suggested as an atherosclerotic index in patients with type 2 diabetes and a useful parameter to assess insulin resistance in patients with and without diabetes. Methods-We investigated, therefore, the relationship between L:A ratio and intima media thickness (IMT), an independent predictor of cardiovascular disease, in 110 healthy males. Results-L:A ratio was significantly correlated to body mass index, waist, hip, waist-to-hip ratio, systolic blood pressure, IMT, high-density lipoprotein, apolipoprotein A-I, glucose, and the homeostasis model of insulin resistance-revised. No significant correlation was observed with age, diastolic blood pressure, low-density lipoprotein, triglycerides, apolipoprotein B, ApoB/ApoA-I ratio, insulin, alanine transaminase, ␥-glutamyl-transferase, and resistin. In addition, when the relationship between IMT and adiponectin or leptin alone was analyzed, only leptin plasma levels significantly associated with IMT (rϭ0.301, PϽ0.01). In a multiple regression analysis including in the statistical model the risk factors known to affect IMT (age, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides, total cholesterol, body mass index, glucose, and L:A ratio), we observed that only age, L:A, and glucose were independent predictors of IMT. As expected, obese subjects (body mass index Ͼ30 kg/m 2 ) showed a significantly higher L:A ratio compared with nonobese subjects (1.20 versus 0.42, respectively, PϽ0.001); in addition, subjects with the metabolic syndrome showed a significantly higher L:A ratio level (0.79) compared with subjects without (0.52) (PϽ0.01). Conclusions-We show here that the L:A ratio is a powerful independent predictor of IMT in healthy subjects and correlates with several anthropometric, metabolic, and clinical parameters better than each single adipokine. (Stroke.

Critically ill patients exhibit reduced melatonin secretion, both in nocturnal peaks and basal daytime levels. Oral melatonin supplementation may be useful for known sedative and antioxidant properties. Its early enteral absorption and daily pharmacokinetics were determined in two cohorts of six high-risk patients in this prospective trial. During their third and fourth Intensive Care Unit (ICU) day, they underwent two different sets of repeated blood samples to detect serum melatonin levels through radio-immuno-assay. Cohort 1: samples taken at 20:00, 20:45, 21:30, 24:00, 03:00, 06:00, 14:00, 20:00 to describe the daily pharmacokinetics. Cohort 2: 20:00, 20:05, 20:10, 20:20, 20:30, 20:45 to study the early absorption. On ICU day 3, endogenous levels were measured, while the absorption of exogenous melatonin was determined on ICU day 4 after administration, at 20:00, of 3 mg melatonin. All basal levels were below the expected values. Following enteral administration, pharmacological levels were already reached in 5 min, with a serum peak after 16 min (half-absorption time: 3 min 17 s). The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half-elimination time of 1 hr 34 min. Serum melatonin levels decreased significantly after midnight; pharmacological levels were maintained up to 10 hr following administration. No excessive sleepiness was reported in this patient group. Critically ill patients exhibited reduced melatonin secretion, as reported in the literature. Despite the critical illness, the oral bioavailability was satisfactory: serum levels after oral administration showed basically unchanged intestinal absorption, while disappearance rate was slower than reported elsewhere in healthy volunteers.

Gonadotropin-releasing hormone (GnRH) neurons are neuroendocrine cells that are born in the nasal placode during embryonic development and migrate through the nose and forebrain to the hypothalamus, where they regulate reproduction. Many molecular pathways that guide their migration have been identified, but little is known about the factors that control the survival of the migrating GnRH neurons as they negotiate different environments. We previously reported that the class 3 semaphorin SEMA3A signals through its neuropilin receptors, NRP1 and NRP2, to organise the axons that guide migrating GnRH neurons from their birthplace into the brain. By combining analysis of genetically altered mice with in vitro models, we show here that the alternative neuropilin ligand VEGF164 promotes the survival of migrating GnRH neurons by co-activating the ERK and AKT signalling pathways through NRP1. We also demonstrate that survival signalling relies on neuronal, but not endothelial, NRP1 expression and that it occurs independently of KDR, the main VEGF receptor in blood vessels. Therefore, VEGF164 provides survival signals directly to developing GnRH neurons, independently of its role in blood vessels. Finally, we show that the VEGF164-mediated neuronal survival and SEMA3A-mediated axon guidance cooperate to ensure that migrating GnRH neurons reach the brain. Thus, the loss of both neuropilin ligands leads to an almost complete failure to establish the GnRH neuron system.

Objective: To evaluate whether a school-based multicomponent educational program could improve adiposity measures in middle-school adolescents. Methods: A non-randomized controlled pilot study was conducted in six state middle schools (487 adolescents, 11-15 years) in townships in an urban area around Milan, three schools (n 5 262 adolescents) being assigned to the intervention group and three schools (n 5 225 adolescents) to the control group. The twoschool-year intervention included changes in the school environment (alternative healthy vending machines, educational posters) and individual reinforcement tools (school lessons, textbook, text messages, pedometers, re-usable water bottles). The main outcome measure was change in BMI z-score. The secondary outcomes were changes in waist-to-height ratio (WHtR) and behavioral habits. Results: The intervention was associated with a significant difference in BMI z-score (20.18 6 0.03, P<0.01) and in WHtR (20.04 6 0.002, P < 0.001), after controlling for baseline covariates. Subgroup analysis showed the maximum association between the intervention and the difference in BMI z-score for girls with overweight/obesity. Physical activity increased and consumption of sugar-sweetened beverages and high-energy snacks decreased in adolescents after the intervention. Conclusions: A school-based multicomponent intervention conducted at both environmental and individual levels may be effective for reducing adiposity measures mainly in adolescents with overweight/obesity.