Temperature can prime human peripheral blood neutrophils in a p38MAPKalpha-dependent manner

INTRODUCTION: Previous ex vivo experiments by others suggest that elevated body temperature can prime the respiratory burst of human neutrophils. The mechanism of the priming phenomenon induced by temperature has not been addressed so far. Furthermore, the priming temperature range was not defined. MATERIAL/METHODS: In the present study we explored ,under in vitro conditions, the influence of febrile-range temperatures on reactive oxygen species (ROS)generation by human peripheral blood neutrophils. ROS production was measured using whole.blood luminol-dependent chemiluminescence. Two elements of signal transduction pathways, calcium and p38 mitogen.activated protein kinase alpha (p38MAPKalpha) ,frequently underlying neutrophil priming were also examined.Calcium levels in the cytosol of resting and fMLP. stimulated isolated neutrophils were measured with the Fura-2AM spectrofluorimetric method. The activity of p38MAPKalpha was assessed indirectly with a specific inhibitor of the kinase, SB 203580. RESULTS: The study revealed a priming effect at 38 degrees C toward human peripheral blood neutrophil ROS production. Any concomitant effect on calcium response was not observed. Instead, experiments with SB 203580,a specific inhibitor of p38MAPKalpha, pointed to an increased activity of the kinase as a molecular background of temperature-induced priming. However, the priming effect of temperature was confined to 38 degrees C, while higher temperatures proved to exert no effect (39 and 40 degrees C)or even inhibited ROS generation by neutrophils (43 degrees C). CONCLUSIONS: Our study suggests a heterogeneous influence of temperature on human neutrophil functioning, including the priming of the cells by a low-febrile-range temperature. It also suggests a p38MAPKalpha-dependent molecular background of the priming phenomenon.     

Evidence that orexins A and B stimulate insulin secretion from rat pancreatic islets via both receptor subtypes

Orexins are recently identified neuropeptides that appear to play a role in the regulation of energy homeostasis and arousal. They bind to and activate two closely related G protein-coupled receptors (OXR1 and OXR2), previously described as orphans. In this study we examined involvement of orexins in regulation of insulin secretion from rat pancreatic islets utilizing an in situ perfused pancreas and isolated pancreatic islet models. By means of RT-PCR we found that both OXR1 and OXR2 are expressed in rat pancreatic islets. Furthermore, the expression levels of OXR1 were higher than OXR2. In both experimental models applied, orexins A and B (1, 10 and 100 nmol/l) concentration dependently stimulated insulin secretion at two different glucose concentrations (6.66 or 26.4 mmol/l), with orexin A being more potent than orexin B. This study demonstrates that orexins A and B modulate insulin secretion in vitro.     

Assessing the effects of bupropion SR on mood dimensions of depression

BACKGROUND: We assessed the therapeutic effects of bupropion SR and placebo on mood and anxiety symptoms derived from the tripartite model of mood. Based on evidence indicating linkages between dopaminergic activity and the emotional dimension of positive affect/anhedonia, we hypothesized that the dopaminergic effects of bupropion SR would yield particularly pronounced effects on symptoms of anhedonia, relative to anxiety. METHODS: Nineteen depressed outpatients were randomly assigned to treatment with either bupropion SR 300 mg/day or placebo during a 6-week initial treatment phase. This was followed by a second open-label phase in which patients previously treated with bupropion SR had their dose increased to 400 mg/day, and the placebo group was initiated on bupropion SR 300 mg/day. RESULTS: Random regression analyses revealed that during the initial double-blind phase, bupropion SR elicited greater declines than placebo on all measures except those that assessed anxiety. By contrast, the weakest placebo effects were evident on anhedonia. Items assessing the low positive affect pole of the anhedonia dimension were more sensitive to earlier/lower dose bupropion SR treatment, whereas items assessing the high positive affect pole were more sensitive to later/higher dose bupropion SR treatment. LIMITATIONS: Replication and extension using a larger sample size are mandated. CONCLUSIONS: This study suggests that the catecholaminergic effects of bupropion SR tended to produce more robust effects on anhedonia/positive affect than placebo.     

Target-to-target interval versus probability effects on P300 in one- and two-tone tasks

The P3(00) is an electrophysiological index of neural processing that varies with such stimulus parameters as interstimulus interval (ISI) and target probability, with a common view being that it reflects an endogenous form of memory update. Building on previous research, we argue that relations between P3 amplitude and both ISI and probability may be attributable to the target-to-target interval (TTI). Employing between-subject (Experiment 1; N = 24) and within-subject (Experiment 2; N = 10) designs, the present paper addresses this by testing subjects on a standard two-tone auditory oddball task as well as a one-tone task. In both studies, P3 amplitude increased and latency decreased linearly with TTI, and these relations were relatively unaffected by ISI or probability. This suggests that ISI and probability per se do not independently affect P3 amplitude, and that TTI offers a strong explanation of the reported relations between P3 amplitude and both ISI and probability.     

Specific Pseudomonas Immunoglobulin E Antibodies in Sera of Patients with Cystic Fibrosis

Immunoglobulin E antibodies to Psuedomonas aeruginosa were demonstrated in patients with cystic fibrosis colonized with the bacterium.     

Learning of olfactory cues is not necessary for early lamb recognition by the mother

Ewes identify their young through the use of different sensory modalities. Olfactory recognition, which mediates selective acceptance at the udder, is established at 4 h postpartum (pp). Visual and auditory cues are involved in recognition at a distance, which is evident at 12 h pp. This study investigates whether anosmic ewes are able (a) to develop visual and auditory recognition and (b) to restore selective acceptance of their lamb at the udder. Visual and auditory recognition was assessed in anosmic and intact ewes at 12 h and 24 h pp by a test of two choices: their own and an alien lamb. Selectivity at allowing suckling was tested by presenting successively an alien and the familiar lamb at 4 h, 3 days, and 1 month pp. In the two-choice recognition test, at both 12 h and 24 h pp, anosmic as well as intact ewes showed a preference for their familiar lamb. Although anosmic ewes showed no difference in their acceptance of alien and familiar lambs for suckling at 4 h and 3 days pp, they nursed the alien lamb less at 1 month pp and showed more rejection behaviors toward it. Thus, visual, auditory, or both those types of recognition can be rapidly established, independent of olfactory recognition. Moreover, differential behavior of anosmic ewes toward their own versus an alien lamb at the udder at 1 month suggests that vision and audition may compensate to some extent for the loss of olfaction.     

CD8 memory, immunodominance, and antigenic escape

Previous theoretical work has suggested that efficient virus control or clearance requires antigen-independent persistence of memory cytotoxic T lymphocyte precursors (CTLp), and that failure to generate such memory CTLp can result in persistent infection and eventual loss of virus control. Here we use mathematical models to investigate the relationship between virus control, the clonal composition of the CTL response and the chance of the virus to evolve antigenic escape. In the presence of efficient memory CTLp, virus is controlled at very low levels by a broad CTL response directed against multiple epitopes. In this case, antigenic escape of the virus population is expected to take a very long time. On the other hand, if the CTL response is short lived in the absence of antigen, virus replicates at higher levels and is only opposed by a narrow CTL response, characterized by an immunodominant CTL clone. In this case, antigenic escape is expected to evolve in a short period of time, resulting in progressive loss of virus control. We discuss our findings in relation to data from HIV-1-infected patients.     

Immune and autoimmune aspects of diabetes mellitus

The immune and autoimmune aspects of diabetes mellitus are reviewed. Emphasis is given to the clinical association of diabetes with other autoimmune disease; the increased incidence of organ-specific autoimmunity in diabetic patients; the occurrence of humoral and cell-mediated antipancreas (islet) autoimmunity in diabetes; the association of HLA with juvenile-onset, insulin-dependent diabetes mellitus and with certain specific subpopulations of diabetic patients; the possible role of viruses in the etiology of diabetes; and the occurrence of alterations in humoral and cell-mediated immunity, granulocyte function, and the host defense against infectious agents in human diabetics and in animals with experimental diabetes.     

Influence of indomethacin and of prostaglandin E1 on total and regional blood flow in man

The central and regional circulatory effects in man of the prostaglandin synthetase inhibitor indomethacin and of prostaglandin E1 (PGE1) were studied. Systemic blood pressure, cardiac output, and renal and splanchnic blood flow were measured at rest, following infusion of indomethacin (50 mg i.v.), and during infusion of PGE1 (4--8 mg x min-1 i.v.) after the administration of indomethacin. An increase in the total systemic resistance (+ 20%), as well as in the renal (+ 30%) and splanchnic (+ 16%) vascular resistances developed rapidly following the administration of indomethacin. Infusion of PGE1 completely restored the resistance in the renal and splanchnic regions, and in addition markedly increased the blood flow in non-visceral tissues. We suggest that the circulatory effects by indomethacin are elicited via the drug's inhibitory effect on prostaglandin synthetase in the vessel walls, and that vasodilating products of PG synthetase affect the regional blood flow distribution in man.