Leptin Controls Parasympathetic Wiring of the Pancreas during Embryonic Life

The autonomic nervous system plays a critical role in glucose metabolism through both its sympathetic and parasympathetic branches, but the mechanisms that underlie the development of the autonomic innervation of the pancreas remain poorly understood. Here, we report that cholinergic innervation of pancreatic islets develops during mid-gestation under the influence of leptin. Leptin-deficient mice display a greater cholinergic innervation of pancreatic islets beginning in embryonic life, and this increase persists into adulthood. Remarkably, a single intracerebroventricular injection of leptin in embryos caused a permanent reduction in parasympathetic innervation of pancreatic β cells and long-term impairments in glucose homeostasis. These developmental effects of leptin involve a direct inhibitory effect on the outgrowth of preganglionic axons from the hindbrain. These studies reveal an unanticipated regulatory role of leptin on the parasympathetic nervous system during embryonic development and may have important implications for our understanding of the early mechanisms that contribute to diabetes

Diagnosis of Cardiac Device–Related Infective Endocarditis After Device Removal

ObjectivesWe sought to determine the incidence, diagnostic value, and outcome of intracardiac masses observed by echocardiography after device removal. We hypothesized that these “ghosts” of leads could be associated with the diagnosis of cardiac device–related infective endocarditis (CDRIE).BackgroundThe echocardiographic appearance of residual floating masses in the right atrium after removal of permanent pacemakers and implantable cardioverter-defibrillators was recently described. However, the significance of these ghosts and their relationship with CDRIE are unknown.MethodsThe pre-operative clinical, microbiological, and echocardiographic conditions; the indication; and the removal technique were analyzed in a retrospective cohort including all consecutive patients who underwent percutaneous lead removal. Three groups were formed according to the final diagnosis: CDRIE, local device infection, and noninfectious indications. The incidence of ghosts was compared among the 3 groups. All clinical, infectious, and extraction-related factors were studied for their association with ghosts. All patients with ghosts were followed after hospitalization.ResultsTwo hundred twelve patients underwent lead removal. Ghosts were observed in 17 patients (8% incidence), including 14 (16%) of 88 patients with CDRIE and 3 (5%) of 59 patients with local device infection. Ghosts were never observed among the remaining 65 noninfected patients. A significant association was found between CDRIE and the presence of a ghost (odds ratio: 7.63, 95% confidence interval: 2.12 to 27.45, p = 0.001). At 3 months, 2 patients with ghosts died suddenly, 2 underwent surgery, and 1 had a pulmonary embolism.ConclusionsGhosts are observed in 8% of patients after percutaneous device extraction. Their presence is suggestive of device infection and seems to be associated with the diagnosis of CDRIE. The prognostic significance of such findings needs further investigation

Use of the intramuscular route to administer pentamidine isethionate in Leishmania guyanensis cutaneous leishmaniasis increases the risk of treatment failure

International audienceBackground: New world cutaneous leishmaniasis (NWCL) can be found in French Guiana as well as in several other parts of Central and South America. Leishmania guyanensis accounts for nearly 90% of cases in French Guiana and is treated with pentamidine isethionate, given by either intramuscular or intravenous injection. The military population is particularly exposed due to repeated missions in the rainforest. The purpose of the present study was to identify the factors associated with pentamidine isethionate treatment failure in a series of service members with L. guyanensis NWCL acquired in French Guiana. Method: All the French service members reported as having acquired leishmaniasis in French Guiana from December 2013 to June 2016 were included. Results: Seventy-three patients infected with L. guyanensis were included in the final analysis. Patients treated with IV pentamidine isethionate had better response rates than those treated with IM pentamidine isethionate (p = 0.002, adjusted odds ratio (AOR) = 0.15, 95% CI [0.04-0.50]). The rate of treatment success was 85.3% (95% CI [68.9-95.0]) for IV pentamidine isethionate and 51.3% (95% CI [34.8-67.6]) for IM pentamidine isethionate. Conclusions: The use of intramuscular pentamidine isethionate in the treatment of Leishmania guyanensis cutaneous leishmaniasis is associated with more treatment failures than intravenous pentamidine isethionate

Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction

International audienceThe transition to puberty and adult fertility both require a minimum level of energy availability. The adipocyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and are infertile. Restoration of leptin levels in these individuals promotes sexual maturation, which requires the pulsatile, coordinated delivery of gonadotropin-releasing hormone to the pituitary and the resulting surge of luteinizing hormone (LH); however, the neural circuits that control the leptin-mediated induction of the reproductive axis are not fully understood. Here, we found that leptin coordinated fertility by acting on neurons in the preoptic region of the hypothalamus and inducing the synthesis of the freely diffusible volume-based transmitter NO, through the activation of neuronal NO synthase (nNOS) in these neurons. The deletion of the gene encoding nNOS or its pharmacological inhibition in the preoptic region blunted the stimulatory action of exogenous leptin on LH secretion and prevented the restoration of fertility in leptin-deficient female mice by leptin treatment. Together, these data indicate that leptin plays a central role in regulating the hypothalamo-pituitary-gonadal axis in vivo through the activation of nNOS in neurons of the preoptic region

Online Aerosol Chemical Characterization by Extractive Electrospray Ionization-Ultrahigh-Resolution Mass Spectrometry (EESI-Orbitrap)

Current mass spectrometry techniques for the online measurement of organic aerosol (OA) composition are subjected to either thermal/ionization-induced artifacts or limited mass resolving power, hindering accurate molecular characterization. Here, we combined the soft ionization capability of extractive electrospray ionization (EESI) and the ultrahigh mass resolution of Orbitrap for real-time, near-molecular characterization of OAs. Detection limits as low as tens of ng m(-3) with linearity up to hundreds of mu g m(-3) at 0.2 Hz time resolution were observed for single- and mixed-component calibrations. The performance of the EESI-Orbitrap system was further evaluated with laboratorygenerated secondary OAs (SOAs) and filter extracts of ambient particulate matter. The high mass accuracy and resolution (140 000 at m/z 200) of the EESI-Orbitrap system enable unambiguous identification of the aerosol components' molecular composition and allow a clear separation between adjacent peaks, which would be significantly overlapping if a medium-resolution (20 000) mass analyzer was used. Furthermore, the tandem mass spectrometry (MS2) capability provides valuable insights into the compound structure. For instance, the MS2 analysis of ambient OA samples and lab-generated biogenic SOAs points to specific SOA precursors in ambient air among a range of possible isomers based on fingerprint fragment ions. Overall, this newly developed and characterized EESI-Orbitrap system will advance our understanding of the formation and evolution of atmospheric aerosols

Neuropilin-1 expression in GnRH neurons regulates prepubertal weight gain and sexual attraction.

Hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH), the "master molecule" regulating reproduction and fertility, migrate from their birthplace in the nose to their destination using a system of guidance cues, which include the semaphorins and their receptors, the neuropilins and plexins, among others. Here, we show that selectively deleting neuropilin-1 in new GnRH neurons enhances their survival and migration, resulting in excess neurons in the hypothalamus and in their unusual accumulation in the accessory olfactory bulb, as well as an acceleration of mature patterns of activity. In female mice, these alterations result in early prepubertal weight gain, premature attraction to male odors, and precocious puberty. Our findings suggest that rather than being influenced by peripheral energy state, GnRH neurons themselves, through neuropilin-semaphorin signaling, might engineer the timing of puberty by regulating peripheral adiposity and behavioral switches, thus acting as a bridge between the reproductive and metabolic axes