Plasma vasopressin and interpersonal functioning

The neuropeptide vasopressin has traditionally been associated with vasoconstriction and water reabsorption by the kidneys. However, data from experimental animal studies also implicate vasopressin in social bonding processes. Preliminary work suggests that vasopressin also plays a role in social behaviors in humans. The goal of this cross-sectional study was to evaluate associations among plasma vasopressin and self-reported interpersonal functioning in a sample of married couples. During a 24-h admission to a hospital-based research unit, 37 couples completed measures of interpersonal functioning and provided blood samples for neuropeptide analyses. Results showed that vasopressin was associated with markers of interpersonal functioning, but not with general psychological distress. Specifically, greater plasma vasopressin levels were related to a larger social network, fewer negative marital interactions, less attachment avoidance, more attachment security, and marginally greater spousal social support. These results indicate that vasopressin is likely implicated in different relationship maintenance processes in humans.     

Ultrasound Measures of Brain Pulsatility Correlate with Subcortical Brain Volumes in Healthy Young Adults

Increasing evidence suggests that brain pulsatility is involved in the pathophysiology of various neurological and psychiatric disorders. However, it remains unclear whether high brain pulsatility is damaging to or protective of the brain in normal conditions, and this could depend on the age of the individual and the methods used to measure brain pulsatility. The goal of our study was to investigate associations between subcortical volumes and brain pulsatility as assessed with ultrasound in healthy young adults using both a conventional method (transcranial Doppler pulsatility index [TCD-PI]) and the innovative method of tissue pulsatility imaging (TPI), which allows a high level of detection of small brain movements (micrometers). Twenty-five females aged 18–55 with no history of significant medical disorder underwent magnetic resonance imaging and ultrasound assessment. The volumes of six subcortical regions known to be particularly sensitive to change in cerebral blood flow were measured and compared with brain pulsatility as assessed with TCD-PI and TPI. TCD-PI and TPI measures positively correlated with all subcortical regions, with the caudate nucleus having the strongest association. Linear regressions found that TCD-PI and TPI measures of brain pulsatility explained 16% to 67% of the variance of the subcortical volumes. Our results suggest that a greater pulsatility as assessed with ultrasound in healthy young adults may constitute a protective factor for brain structure. Ultrasound measures of brain pulsatility may be appropriate to provide costless, non-invasive, portable and highly sensitive markers of cerebral blood flow pulsatility related to brain structure.     

Overcoming EMT-associated resistance to anti-cancer drugs via Src/FAK pathway inhibition

Epithelial to mesenchymal transition (EMT) is a key process in embryonic development and has been associated with cancer metastasis and drug resistance. For example, in EGFR mutated non-small cell lung cancers (NSCLC), EMT has been associated with acquired resistance to the EGFR inhibitor erlotinib. Moreover, “EGFR-addicted” cancer cell lines induced to undergo EMT become erlotinib-resistant in vitro. To identify potential therapeutic vulnerabilities specifically within these mesenchymal, erlotinib-resistant cells, we performed a small molecule screen of ~200 established anti-cancer agents using the EGFR mutant NSCLC HCC827 cell line and a corresponding mesenchymal derivative line. The mesenchymal cells were more resistant to most tested agents; however, a small number of agents showed selective growth inhibitory activity against the mesenchymal cells, with the most potent being the Abl/Src inhibitor, dasatinib. Analysis of the tyrosine phospho-proteome revealed several Src/FAK pathway kinases that were differentially phosphorylated in the mesenchymal cells, and RNAi depletion of the core Src/FAK pathway components in these mesenchymal cells caused apoptosis. These findings reveal a novel role for Src/FAK pathway kinases in drug resistance and identify dasatinib as a potential therapeutic for treatment of erlotinib resistance associated with EMT.     

Adéquation en dialyse péritonéale : mise au point

The optimal method to assess the adequacy of peritoneal dialysis therapies is controversial. Today, the adequacy must not be considered as a number or a concept assessed only by two parameters (total KT/V urea and total solute clearance) but defined by many more items. In the absence of data, based on theoretical considerations, the reanalysis of the CANUSA study showed that renal kidney function, rather than peritoneal clearance, was associated with improved survival. Residual renal function is considered as a major predictor factor of cardiovascular mortality. Results of this reanalysis were supported by the adequacy data in ADEMEX, EAPOS and ANZDATA studies. Therefore, clinical assessment plays a major role in PD adequacy. The management of fluid balance, the regular monitoring of malnutrition, the control of mineral metabolism and particularly the glucose load, considered as the “corner-stone” of the system, are the main points to be considered in the adequacy of PD patients. The essential goal is to minimize glucose load by glucose-sparing strategies in order to reduce the neoangiogenesis of the peritoneal membrane.