Evidence for direct interaction between mast cells and Leishmania parasites

When stimulated through IgE- (or IgG-) immune complexes with parasite antigens, mast cells can release several cytokines, including IL-4, IL-6, IL-10, IL-12, Interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) that may influence the host response to Leishmania major in modulating lesion size and persistence during experimental infection in the mouse. Moreover, recent data demonstrated that mast cells are able to be antibody-independently activated by direct contact with bacteria, making them important elements in innate immunity. Given these data, we asked whether cell-parasite contact could directly induce mast cell mediator release and whether mast cells could be infected by L. major or L. infantum parasites.    In this study, we showed that a pure homogeneous population of mouse bone marrow derived mast cells (BMMC) in contact with living L. major or L. infantum promastigotes, but not with attenuated parasites or soluble parasite antigens, released preformed mediators such as β-hexosaminidase and the preformed pool of TNF-α within minutes. Furthermore, direct cell-parasite contact induced TNF-α synthesis by mast cells within hours. Moreover, we demonstrated by in vitro co-culture experiments that metacyclic L. major or L. infantum promastigotes are directly infective for a significant proportion of BMMC and are transformed into intracellular amastigotes. Taken together, these data suggest that mast cell can participate in the first line of defence, i.e. innate immunity, during local cutaneous infection with Leishmania parasites.     

Stimulus dimensions of the cold pressor test and the associated patterns of cardiovascular response

Hemodynamics of the cold pressor response in relation to its pain and nonpain stimulus components were investigated in normotensive college men using the foot and forehead cold pressor tasks. Mechanisms of pain- and non-pain-related increases in blood pressure were analyzed as residual effects of concurrent changes in total peripheral resistance and cardiac output. The identified partial relationships suggested that the response pattern associated with pain included positive change both in cardiac output and in total peripheral resistance, whereas the nonpain-related response was limited to an increase in total peripheral resistance. Analyses of individual differences in car-diovascular responses to pain further indicated that pain-related increments in blood pressure were mediated by a steeper rise in total peripheral resistance, an increase in heart rate, and an apparent increase in preload. At baseline, high reactors to pain manifested relatively elevated total perpheral resistance, diminished cardiac output, and an indication of a reduced inotropic state, suggesting that altered basal homeostasis may discriminate normotensive individuals displaying heightened cardiovascular reactivity to aversive cold stimulation.     

A combined neuropsychological and brain imaging study of obstructive sleep apnea

Patients with obstructive sleep apnea (OSA) show neuropsychological impairments ranging from vigilance decrements, attentional lapses and memory gaps to decreased motor coordination, but their cognitive profile, and the origin of the impairments, remain unclear. We sought to establish the neuropsychological profile of 16 newly diagnosed apneics and to highlight both their morphological and functional brain abnormalities. We used an extensive neuropsychological test battery to investigate attention and vigilance, executive functions, episodic memory and motor domains. For brain imaging, we used the optimized voxel-based morphometry procedure for the MRI data, resting-state ¹⁸F-fluoro-2-deoxy-D-Glucose positron emission tomography (¹⁸FDG-PET) with correction for partial volume effects (PVEs) and voxel-based analyses. In terms of neurobehavioral performance, our patients displayed objective daytime somnolence but little impairment in memory and motor domains. Cerebral data revealed gray matter loss in the frontal and temporo–parieto–occipital cortices, the thalamus, hippocampal region, some basal ganglia and cerebellar regions, mainly in the right hemisphere. The decrease in brain metabolism was also right-lateralized, but more restricted than the gray matter density changes, and involved the precuneus, the middle and posterior cingulate gyrus, and the parieto–occipital cortex, as well as the prefrontal cortex. To conclude, despite the presence of only minor memory and motor impairments, our patients displayed significant cerebral changes in terms of both gray matter density and metabolic levels, and may have benefited from cognitive reserve and compensatory mechanisms. Thus, cerebral changes in OSA patients may precede the onset of notable neuropsychological consequences.