Fatigue and breastfeeding: an inevitable partnership?

Postpartum fatigue is a normal condition that most women experience. Breastfeeding is often associated in women's minds as contributing to the feeling of overall perceived fatigue, and many women indicate that they have ceased breastfeeding because of fatigue. However, the relationship between feeding choice and perceived fatigue has never been established. Two hundred and fifty-three women participated in a study examining whether perceived fatigue differed for bottle-feeding and breastfeeding women at 3 different times during the postpartum period (2-4 days, 6 weeks, and 12 weeks postpartum). Results showed no significant differences for these 2 groups, suggesting that perceived fatigue during the postpartum period is not dependent on feeding choice. Additional analyses examining other variables with a potential effect were nonsignificant. Because perceived physical fatigue does not appear to be dependent on feeding choice, women should be prepared for the feeling of perceived fatigue during the postpartum period while at the same time be reassured that feeding choice is not correlated.     

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.     

HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.     

Blood velocity assessment using 3D bright-blood time-resolved magnetic resonance angiography.

Blood velocity is a functional parameter that is not easily assessed noninvasively, especially in small animals. A new noninvasive method that uses magnetic resonance angiography (MRA) to measure blood flows is proposed. This method is based on the time-of-flight (TOF) phenomenon. By initially suppressing the signal from the stationary spins in the area of interest, it is possible to sequentially visualize only the signal from the moving spins entering a given volume. With this method, 3D cine images of the blood flow can be generated by positive contrast, with unparalleled spatial (<200 microm) and temporal resolutions (<10 ms/image). As a result, it is possible to measure flow in sinuous paths. The present method was applied in vivo to measure the blood velocity in mouse carotid arteries. Because of its robustness and simplicity of implementation, this method has numerous potential applications for fundamental studies in small animal models.     

Behavioral measurement of axonal thresholds

A behavioral method for measuring the electrical sensitivity of directly stimulated elements in the brain is described and applied to the medial forebrain bundle (MFB) reward path and the tectospinal circling path. Equations are derived from which threshold current densities may be calculated from knowledge of the electrode tip dimensions and the current required to produce criterion behavior, which is a function of electrode size. Four different sizes of electrode were implanted in the MFB of rats and self-stimulation rates plotted against stimulating current. The mean currents for criterion bar-pressing rates of 25% and 55% of maximum rate were determined for each electrode size and the values used to calculate average threshold current densities. Two sizes of electrode were implanted in the tectospinal tract of rats and the average currents to produce circling at 0.2 and 0.4 turns/s were measured. The threshold current densities for self-stimulation axons were about 5 times as large as those for circling, in accordance with other evidence that tectal circling path axons are larger than those of the MFB reward path.     

Greater efficacy of pulsatile insulin in type I diabetics critically depends on plasma glucagon levels

The aim of this study was to investigate the role of plasma glucagon levels on the blood glucose response to intravenous insulin administered continuously or in a pulsatile manner. Six type I diabetic patients proven to have no residual insulin secretion were investigated. Endogenous glucagon secretion was inhibited by a continuous intravenous infusion of somatostatin (100 micrograms/h) and replaced by exogenous infusions of the hormone at three different rates (7.5, 4.5, and 2.5 micrograms/h), resulting in three different plasma glucagon steady-state levels (i.e., approximately equal to 200, approximately equal to 130, and approximately equal to 75 pg/ml, respectively). Each subject, in random order and on different days, was infused intravenously with regular human insulin either continuously (0.17 mU X kg-1 X min-1) or with the same amount of insulin infused in a pulsatile manner (0.85 mU X kg-1 X min-1 during 2 min followed by 8 min during which no insulin was infused). At plasma glucagon levels approximately equal to 200 pg/ml, blood glucose rose from approximately 10 to approximately 13 mM without any difference between the two modalities of insulin infusion. For plasma glucagon levels approximately equal to 130 pg/ml, plasma glucose remained steady throughout the experiments, but during the last 40 min, plasma glucose levels were significantly lower when insulin was administered intermittently. This greater blood glucose-lowering effect of pulsatile insulin occurred earlier and was more pronounced for plasma glucagon levels averaging 75 pg/ml. We conclude that the greater hypoglycemic effect of insulin administered intravenously in a pulsatile manner in type I diabetics critically depends on plasma glucagon circulating levels.