Effects of recovery duration and time of day on sprint performance]

Effects of recovery duration (2-3 s, 15 s, 30 s, 1 min, and 2 min) and time of day (9 a.m., 2 p.m., and 6 p.m.) on sprint performance were studied in 9 subjects using a cycle ergometer. The peak power (Ppeak) and the total work performed (W) were determined from changes in instantaneous power, taking into account the inertia of the flywheel. A decrease in Ppeak and W was observed after 15 s and 2-3 s recovery (p < 0.001). A logarithmic relationship (y = 3.92 ln x + 81.5; r = 0.82; n = 9) was found between Ppeak (%Ppeak of the first sprint) and the duration of the recovery (half-time = 14.3 s; SD = 7.6). Data indicated that there was no significant effect of time of day on Ppeak and W, regardless of the duration of recovery. The recovery processes occurred in a very short time and did not seem to be affected by biological rhythms.     

Vasoactive Intestinal Peptide Maintains the Nonpathogenic Profile of Human Th17-Polarized Cells

The cytokine microenvironment modulates CD4 T cell differentiation causing the shift of naïve CD4 T cells into different cell subsets. This process is also regulated by modulators such as vasoactive intestinal peptide (VIP), a neuropeptide with known immunomodulatory properties on CD4 T cells that exert this action through specific receptors, vasoactive intestinal peptide receptor (VPAC)₁ and VPAC₂. Our results show that the pattern of VIP receptors expression ratio is modified during Th17 differentiation. In this report, we evaluate the capacity of VIP to modulate naïve human cells into Th17 cells in vitro by analyzing their functional phenotype. The presence of VIP maintains the nonpathogenic profile of Th17-polarized cells, increases the proliferation rate, and decreases their Th1 potential. VIP induces the upregulation of the STAT3 gene interaction with the VPAC₁ receptor during the onset of Th17 differentiation. Moreover, RAR-related orphan receptor C (RORC), RAR-related orphan receptor A (RORA), and interleukin (IL)-17A genes are upregulated in the presence of VIP through interaction with VPAC₁ and VPAC₂ receptors. Interestingly, VIP induces the expression of the IL-23R gene through interaction with the VPAC₂ receptor during the expansion phase. This is the first report that describes the differentiation of naïve human T cells to Th17-polarized cells in the presence of VIP and demonstrates how this differentiation regulates the expression of the VIP receptors.     

Impact of manganese on primary hippocampal neurons from rodents

Manganese‐enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo tract tracing or functional imaging of the central nervous system. However Mn²⁺ may be toxic at high levels. In this study, we addressed the impact of Mn²⁺ on mouse hippocampal neurons (HN) and neuron‐like N2a cells in culture, using several approaches. Both HN and N2a cells not exposed to exogenous MnCl₂ were shown by synchrotron X‐ray fluorescence to contain 5 mg/g Mn. Concentrations of Mn²⁺ leading to 50% lethality (LC50) after 24 h of incubation were much higher for N2a cells (863 mM) than for HN (90 mM). The distribution of Mn²⁺ in both cell types exposed to Mn²⁺ concentrations below LC50 was perinuclear whereas that in cells exposed to concentrations above LC50 was more diffuse, suggesting an overloading of cell storage/detoxification capacity. In addition, Mn²⁺ had a cell‐type and dose‐dependent impact on the total amount of intracellular P, Ca, Fe and Zn measured by synchrotron X‐ray fluorescence. For HN neurons, immunofluorescence studies revealed that concentrations of Mn²⁺ below LC50 shortened neuritic length and decreased mitochondria velocity after 24 h of incubation. Similar concentrations of Mn²⁺ also facilitated the opening of the mitochondrial permeability transition pore in isolated mitochondria from rat brains. The sensitivity of primary HN to Mn²⁺ demonstrated here supports their use as a relevant model to study Mn²⁺‐induced neurotoxicity. © 2014 Wiley Periodicals, Inc.     

Twenty-four-hour profiles of urinary excretion of calcium,magnesium, phosphorus,urea, and creatinine in healthy prepubertal boys

ObjectivesAvailable data on 24-h urinary solute excretion in healthy children are sparse. We thus documented the daily and overnight variations of urinary electrolytes (calcium, magnesium, and phosphorus), urea, and creatinine in prepubertal (Tanner stage I) boys.Design and methodsNine voluntary healthy prepubertal boys aged 10.8 ± 0.11 years participated in this study. Concentrations of variables were quantified in daytime samples (collected between 07:00 h ± 30 min and 21:00 h ± 30 min) and nighttime samples (collected between 21:00 h ± 30 min and 07:00 h ± 30 min) in spring, during a period of 24-h every 3 h.ResultsSignificant differences were found between daytime and nighttime excretion of calcium (p < 0.05), magnesium (p < 0.001), phosphorus (p < 0.01), and urea (p < 0.05), with high concentrations during the night. The 24-h solute/creatinine ratio was 0.072 ± 0.008 mg/mg for calcium, 0.069 ± 0.008 mg/mg for magnesium, 0.698 ± 0.070 mg/mg for phosphorus, and 0.017 ± 0.001 g/mg for urea. Statistically significant correlation analyses showed that urea and creatinine were positively associated with body mass index (BMI) (R = 0.790, p = 0.0113 for urea; R = 0.889, p = <0.0013 for creatinine) and weight (R = 0.717, p = 0.0297 for urea; R = 0.978, p = < 0.001 for creatinine). The other urinary variables were independent of BMI and body mass.ConclusionThese data are of interest for the diagnosis of certain renal disease in prepubertal children.     

Age affects pegylated liposomal doxorubicin elimination and tolerability in patients over 70 years old

Purpose

Pegylated liposomal doxorubicin (PLD) is often used in elderly people, due to its improved tolerability. However, clinical and pharmacological data in the subset of patients over 70 are scanty.

Methods

PLD safety was evaluated in 35 patients (aged ≥70 years) who were treated with PLD as a single agent for 165 cycles. Doxorubicin plasma levels, leukocyte DNA breaks and monocyte count variations were measured as markers of drug exposure, DNA repair capability and reticuloendothelial system activation, respectively. A correlation between these markers and age was sought.

Results

Treatment was generally well tolerated. Skin erythrodysesthesia was the most frequent side effect, and no severe (G4) toxicity occurred. PLD plasma half-life generally correlated with age (P < 0.001) and was particularly prolonged in octogenarians (P = 0.005). Doxorubicin clearance significantly declined up to 70 % at cycle 7. DNA breaks increased over the first two cycles (P = 0.007) and were inversely correlated with age (P = 0.007) and directly with clearance (P = 0.006). Pre-treatment monocyte counts increased over cycles (P < 0.001) and were associated with an increase in clearance at cycle 3 (P = 0.015). The hand–foot–skin syndrome was significantly more severe in patients of advanced age or longer PLD half-life.

Conclusions

This study showed (1) increased systemic drug exposure over subsequent cycles; (2) association of age with increased drug exposure, reduced DNA repair capability and worse skin toxicity; (3) a relation between monocyte count and drug clearance.     

Impressive efficacy of sorafenib in a patient with an hepatocellular carcinoma and a portal vein thrombosis associated with a metastatic ENT cancer

Sorafenib, a new antiangiogenic and antiproliferative agent, is currently used for hepatocellular and renal cell carcinoma. We report here the case of a patient with two cancers, a locally advanced cancer of the piriform sinus and a hepatocellular carcinoma, who was given sorafenib. Tumor response of both cancers might suggest that sorafenib could be effective against head and neck cancer.