Oral supplementation with physiological doses of leptin during lactation in rats improves insulin sensitivity and affects food preferences later in life

We have previously described that neonate rats supplemented with physiological doses of oral leptin during lactation become more protected against overweight in adulthood. The purpose of this study was to characterize further the long-term effects on glucose and leptin homeostasis and on food preferences. Neonate rats were supplemented during lactation with a daily oral dose of leptin or the vehicle. We followed body weight and food intake of animals until the age of 15 months, and measured glucose, insulin, and leptin levels under different feeding conditions: ad libitum feeding, 14-h fasting, and 3-h refeeding after fasting. An oral glucose tolerance test and a leptin resistance test were performed. Food preferences were also measured. Leptin-treated animals were found to have lower body weight in adulthood and to eat fewer calories than their controls. Plasma insulin levels were lower in leptin-treated animals than in their controls under the different feeding conditions, as was the increase in insulin levels after food intake. The homeostatic model assessment for insulin resistance index was significantly lower in leptin-treated animals, and the oral glucose tolerance test also indicated higher insulin sensitivity in leptin-treated animals. In addition, these animals displayed lower plasma leptin levels under the different feeding conditions and were also more responsive to exogenous leptin administration. Leptin-treated animals also showed a lower preference for fat-rich food than their controls. These observations indicate that animals supplemented with physiological doses of oral leptin during lactation were more protected against obesity and metabolic features of the metabolic syndrome.     

Los altos volúmenes convectivos se asocian a la mejoría del perfil metabólico en los pacientes diabéticos en hemodiafiltración online

Background and objective

Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF.

Endothelial adhesion molecules ICAM-1, VCAM-1 and E-selectin in patients with acute coronary syndrome

INTRODUCTION AND OBJECTIVES: The acute inflammatory response is an important phenomenon in the pathogenesis of myocardial damage during acute coronary syndrome. Endothelial dysfunction has been found in unstable angina and acute myocardial infarction, although the results are controversial. The purpose of this study was to determine the levels of the soluble endothelial adhesion molecules ICAM-1, VCAM-1 and E-selectin, in patients with unstable angina and acute myocardial infarction, compare the results in both groups, and analyze their relation with the degree of myocardial injury. METHODS: Serum concentrations of ICAM-1, VCAM-1, and E-selectin were measured in 37 control subjects and 43 patients (32 with acute myocardial infarction and 11 with unstable angina). Measurements were made at the time of admission and ten days later using commercial enzyme-linked immunoabsorbent assay (ELISA) kits (R&D Systems, UK). RESULTS: There was a significant increase in E-selectin (p < 0.05) in patients with unstable angina at admission and ten days later. In contrast, patients with acute myocardial infarction showed no significant differences in E-selectin compared with the control group at admission or ten days later. A significant increase in VCAM-1 levels was demonstrated in both groups of patients and ICAM-1 levels in acute myocardial infarction, but the concentrations of VCAM-1 and ICAM-1 in both groups of patients at admission and ten days later did not differ significantly. There was no relation between soluble endothelial adhesion molecule levels and the severity of myocardial damage estimated by cardiac enzymes or electrocardiographic changes. CONCLUSION: This study indicates that serum levels of E-selectin, measured at time of admission and ten days later, could be a marker for unstable angina and might be useful in the differential diagnosis with myocardial infarction.     

Turbulence increases the average settling velocity of phytoplankton cells

It is a well known fact that stirring keeps particles suspended in fluids. This is apparent, for instance, when shaking medicine flasks, when agitating tea deposits in a mug, or when heavy winds fill the air with dust particles. The commonplace nature of such observations makes it easy to accept that this feature will apply to any natural phenomenon as long as the flow is turbulent enough. This has been the case for phytoplankton in the surface mixed layers of lakes and oceans. The traditional view assumes that an increase in turbulence bears ecological advantages for nonmotile groups like diatoms that, otherwise, would settle in deep and unlit waters. However, this assumption has no theoretical ground, and the experimental results we present here point in the opposite direction. Phytoplankton settling velocity increases when turbulence intensifies from the low to the higher values recorded in the upper mixed layers of lakes and oceans. Consequently, turbulence does not favor phytoplankton remaining in lit waters but is rather an environmental stress that can only be avoided through morphological and/or physiological adaptations.     

Gender influence on schizophrenia‐relevant abnormalities in a cuprizone demyelination model

The aim of this study was to determine whether early demyelination can impact behavior in young adulthood. For this purpose, albino Wistar rats of either sex were exposed to cuprizone (CPZ) in two different intoxication protocols: one group was intoxicated before weaning (CPZ‐BW), from postnatal day 7 (P7) to P21, through maternal milk, whereas the other group was intoxicated after weaning (CPZ‐AW), from P21 to P35. After treatment, rats were returned to a normal diet until P90 when behavioral studies were performed. Both treatments produced marked demyelination in the corpus callosum and retraction of cortical myelin fibers. The subsequent normal diet allowed for effective remyelination at P90. Interestingly, CPZ‐AW correlated with significant behavioral and neurochemical changes in a gender‐dependent manner. CPZ‐AW treatment altered both the number of social activities and the latency to the first social interaction in males, while also highly compromising recognition‐related activities. In addition, only P90 males treated AW showed a hyperdopaminergic striatum, confirmed by an increase in tyrosine hydroxylase expression and in dopamine levels. Our results suggest that the timing of demyelination significantly influences the development of altered behavior, particularly in adult males. GLIA 2014;62:1629–1644     

A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial

Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3–6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81–0.91] before the change to 0.32 (95 % CI 0.26–0.40; p < 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p < 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.     

CD207 cells recruitment to the vaccination site and draining lymph nodes after the administration of DC-Apo/Nec vaccine in mice

De novo ectopic lymphoid tissue formation is known to occur in certain disease and inflammatory settings. After an effective vaccination with dendritic cells (DC) charged with melanoma apoptotic/necrotic cells (Apo/Nec), a subcutaneous tertiary lymphoid structure was organized, where retained vaccine cells interacted with recruited inflammatory and T cells. In this work we report for the first time the recruitment of two morphologically different CD207⁺ cells to vaccination site. The time-course behavior of CD207⁺ cells was reciprocal between vaccination site and draining lymph nodes (DLNs). After 6–10 days, CD207⁺ cells localized at the paracortical region of DLNs, in close contact with T cell population. DLNs were enriched in a peculiar MHCII⁺ CD11c⁽⁻⁾ CD207⁺ population, whose role remains to be determined. Whether CD207⁺ cells migration to the vaccination site can be associated with a differential anti-tumoral response remains as an open and exciting question.