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1. Introduction The immune system is a highly complex, intricately regulated group of cells whose integrated function is crucial to health. Cells belonging to the immune system usually interact in [...], The immune system is subject to destruction and dysfunction as a result of attacks by pathogenic and environmental agents. In addition, many clinical situations exist in which it is desirable to stimulate or suppress the immune system. The present study evaluated the screening efficacy of flow cytometric lymphocyte subset typing in peripheral blood mononuclear cells from healthy individuals (HI) and from patients with non-Hodgkin lymphoma (NHL) treated with different concentrations of FR-91, a standardized lysate of microbial cells belonging to the Bacillus genus, and in vitro cytokine production. Increased expression of subset markers (CD3, CD4, CD8) in NHL and CD3 in HI suggests an immunomodulating effect of FR-91. In addition the results of cytokine production also demonstrated a clear effect of FR-91 on both populations. A significant increase of IL-6, IL-12, IFN-γ and TNF-α was observed in the HI group after treatment with FR-91. In a similar manner an increase of IL-2, IL-6, IL-12, IFN-γ and TNF-α was also observed in the NHL group. In conclusion FR-91 seems to affect lymphocyte subpopulations, in vitro cytokine production, as well as mitogen-induced lymphocyte activation in a dose-dependent manner in both healthy individuals and NHL patients. Copyright © 2009 V. R. M. Lombardi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The aim of this investigation was to determine the influence of CFTR genotype on body water and electrolyte balance during a marathon. Fifty-one experienced runners completed a marathon race. Before and after the race, body mass and a sample of venous blood were obtained. During the race, sweat samples were collected using sweat patches, and fluid and electrolyte intake were obtained using self-reported questionnaires. Thirty-eight participants (74.5% of the total) were 7T/7T homozygotes, 11 (21.6%) were 7T/9T heterozygotes, and one participant presented the rare genotype 5T/7T. Another participant with 9T/9T presented the mutation p.L206W. Participants with 7T/7T showed higher sweat sodium concentrations (42.2 ± 21.6 mmol/L) than 7T/9T (29.0 ± 24.7 mmol/L; P = 0.04). The runner with the 5T/7T genotype (10.2 mmol/L) and the participant with the p.L206W mutation (20.5 mmol/L) exhibited low-range sweat sodium concentrations. However, post-race serum sodium concentration was similar in 7T/7T and 7T/9T (142.1 ± 1.3 and 142.4 ± 1.6 mmol/L, respectively; P = 0.27) and did not show abnormalities in participants with the 5T/7T genotype (140.0 mmol/L) and the p.L206W mutation (143.0 mmol/L). Runners with the CFTR-7T/7T genotype exhibited increased sweat sodium concentrations during a marathon. However, this phenotype was not related with increased likelihood of suffering body water and electrolyte imbalances during real competitions. [ABSTRACT FROM AUTHOR]

We have studied the time- and dose-dependent effects of S9977-2 versus tacrine (THA) on psychomotor activity (PMA) and passive avoidance learning (PAL) in intact 3-month-old rats. No significant changes were observed in the levels of PMA in animals tested 0, 30 and 60 min after i.p. injections of S9977-2 (0·125 mg/kg) or THA (1 mg/kg). In a PAL maze paradigm, S9977-2 and THA, administered 30, 60 and 120 min before testing, induced time-dependent improvements in learning indices, with maximum effects during the first hour after administration. In the dose–response study, S9977-2 (0·005, 0·025 and 0·125 mg/kg) tended to increase and THA (0·33, 1 and 3 mg/kg) to decrease PMA scores while the two compounds improved learning in a progressive dose-related manner. The present results indicate that S9977-2 and THA exert opposite actions on exploratory behaviour, S9977-2 increasing this parameter and THA decreasing it, and that both molecules improve learning in a similar time- and dose-dependent manner. On a molar basis S9977-2 is 10–20 times more potent than THA in enhancing learning acquisition. © 1997 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Besides the role of histamine (HA) as a neurotransmitter, a new concept has emerged presenting HA as an immunomodulator. Several studies have demonstrated interactions among HA, interleukin-1 β (IL-1 β) and tumor necrosis factor (TNF), suggesting a possible bidirectional communication among them. In this study we have investigated the effects of i.p. administrations of HA diphosphate (6 µmol/kg) and α-fluoromethylhistidine (FMH; 100 mg/kg) on TNF- α levels in the hippocampus, hypothalamus, and posterior hypothalamic region of the rat brain. The concentrations of TNF- α at 0 (Control, C) and 30 min after i.p. administration of HA were 0.26 ± 0.02 pg/mg and 0.32 ± 0.02 pg/mg in the hippocampus, 0.46 ± 0.04 pg/mg and 0.09 ± 0.006 pg/mg (p < 0.01) in the hypothalamus, and 0.47 ± 0.05 pg/mg and 0.26 ± 0.05 pg/mg in the posterior hypothalamic region. Three hours after FMH administration, an increase in the hippocampal levels of TNF- α was observed (0.43 ± 0.04 pg/mg; p < 0.01), while in the hypothalamus (0.11 ± 0.02 pg/mg; p < 0.01) and in the posterior hypothalamic region (0.21 ± 0.04 pg/mg; p < 0.05) a decrease in TNF- α levels was detected. These results suggest that changes in the histaminergic system influence TNF- α production in the brain in an area-specific fashion. [ABSTRACT FROM AUTHOR]

Some recent studies give support to the potential interaction between histamine (HA) and interleukin-1 (IL-1) in the central nervous system (CNS). At the peripheral level, HA acts as an immune modulator, but little is known on the neuroimmune role of this biogenic amine in the CNS. In the present study we have investigated the effects of HA, mepyramine, famotidine, thioperamide, and L-histidine on hypothalamic IL-1β. HA induced a time- and dose-dependent decrease in the concentration of IL-1β. The maximum effect was obtained 30 minutes after injection. The HA-induced IL-1β response in the hypothalamus was not inhibited by either mepyramine, famotidine or thioperamide. In addition, L-histidine exerted the same effect as HA. The interaction between HA and IL-1β in the CNS might be linked to neuroendocrine regulation as well as to neurotrophic activity and neuroimmune function. [ABSTRACT FROM AUTHOR]

Progressive neuronal loss and cognitive decline in Alzheimer’s disease (AD) might be aggravated by β-amyloid-enhanced excitotoxicity. Memantine is an uncompetitive NMDA receptor antagonist under clinical development for the treatment of AD. Memantine has neuroprotective actions in several in vitro and in vivo models. In the present study, we determined whether memantine protected against β-amyloid induced neurotoxicity and learning impairment in rats. Twenty Sprague–Dawley rats received vehicle or vehicle plus memantine (steady-state plasma concentrations of 2.34±0.23 μM, n=10) s.c. by osmotic pump for 9 days. After 2 days of treatment, 2 μl of water containing β-amyloid 1–40 [Aβ(1–40)] were injected into the hippocampal fissure. On the ninth day of treatment, animals were sacrificed, and morphological and immunohistochemical techniques were used to determine the extent of neuronal degeneration and astrocytic and microglial activation in the hippocampus. Psychomotor activity and spatial discrimination were tested on the eighth day of treatment. Aβ(1–40), but not water, injections into hippocampus led to neuronal loss in the CA1 subfield, evidence of widespread apoptosis, and astrocytic and microglial activation and hypertrophy. Memantine treated animals had significant reductions in the amount of neuronal degeneration, pyknotic nuclei, and GFAP immunostaining as compared with vehicle treated animals. These data suggest that memantine, at therapeutically relevant concentrations, can protect against neuronal degeneration induced by β-amyloid. [Copyright &y& Elsevier]