The method of UCN "small heating" measurement in the big gravitational spectrometer (BGS) and studies of this effect on Fomblin oil Y-HVAC 18/8.

The Big Gravitational Spectrometer (BGS) takes advantage of the strong influence of the Earth's gravity on the motion of ultracold neutrons (UCNs) that makes it possible to shape and measure UCN spectra. We optimized the BGS to investigate the "small heating" of UCNs, that is, the inelastic reflection of UCNs from a surface accompanied by an energy change comparable with the initial UCN energy. UCNs whose energy increases are referred to as "Vaporized UCNs" (VUCNs). The BGS provides the narrowest UCN spectra of a few cm and the broadest "visible" VUCN energy range of up to ∼150 cm (UCN energy is given in units of its maximum height in the Earth's gravitational field, where 1.00 cm ≈ 1.02 neV). The dead-zone between the UCN and VUCN spectra is the narrowest ever achieved (a few cm). We performed measurements with and without samples without breaking vacuum. BGS provides the broadest range of temperatures (77-600 K) and the highest sensitivity to the small heating effect, up to ∼10-8 per bounce, i.e., two orders of magnitude higher than the sensitivity of alternative methods. We describe the method to measure the probability of UCN "small heating" using the BGS and illustrate it with a study of samples of the hydrogen-free oil Fomblin Y-HVAC 18/8. The data obtained are well reproducible, do not depend on sample thickness, and do not evolve over time. The measured model-independent probability P+ of UCN small heating from an energy "mono-line" 30.2 ± 2.5 cm to the energy range 35-140 cm is in the range 1.05±0.02stat×10-5-1.31±0.24stat×10-5 at a temperature of 24 °C. The associated systematic uncertainty would disappear if a VUCN spectrum shape were known, for instance, from a particular model of small heating. This experiment provides the most precise and reliable value of small heating probability on Fomblin measured so far. These results are of importance for studies of UCN small heating as well as for analyzing and designing neutron lifetime experiments.

The effects of polycyclic aromatic hydrocarbons on the immune system of fish: a review.

Polycyclic aromatic hydrocarbons are an important class of environmental pollutants that are known to be carcinogenic and immunotoxic. This review summarizes the diverse literature on the effects of these pollutants on innate and acquired immunity in fish and the mechanism of PAH-induced immunotoxicity. Among innate immune parameters, many authors have focused on macrophage activities in fish exposed to polycyclic aromatic hydrocarbons. Macrophage respiratory burst appears especially sensitive to polycyclic aromatic hydrocarbons. Among acquired immune parameters, lymphocyte proliferation appears highly sensitive to polycyclic aromatic hydrocarbon exposure. However, the effects of polycyclic aromatic hydrocarbons on both specific and non-specific immunity are contradictory and depend on the mode of exposure, the dose used or the species studied. In contrast to mammals, fewer studies have been done in fish to determine the mechanism of polycyclic aromatic hydrocarbon-induced toxicity. This phenomenon seems to implicate different intracellular mechanisms such as metabolism by cytochrome P4501A, binding to the Ah-receptor, or increased intracellular calcium. Advances in basic knowledge of fish immunity should lead to improvements in monitoring fish health and predicting the impact of polycyclic aromatic hydrocarbons on fish populations, which is a fundamental ecotoxicological goal.

Possible implication of macrophages in the regulation of cytochrome P450 activities in carp (Cyprinus carpio).

Macrophages play a key role in the regulation of cytochrome P450 activity induced by immunostimulants in mammals. We investigated the effects of immunostimulants (LPS, dextran sulfate and tilorone) on biotransformation and macrophage activities in carp. The major effect of LPS was its capacity to inhibit 3-MC-induced cytochrome P450 activities in the liver and head kidney. Basal phase I activities were reduced by tilorone and dextran sulfate in immune organs. Tilorone and dextran sulfate differently modulated total cytochrome P450 contents and P4501A activities suggesting differential sensitivity for P450 classes. In immune organs, tilorone and dextran sulfate inhibited basal EROD activity. Tilorone inhibited 3-MC-induced EROD activity whereas dextran sulfate enhanced this activity. LPS and dextran sulfate increased ROS production by macrophages and all the immunostimulants induced macrophage activating factor (MAF) production. This study demonstrates for the first time in fish the capacity of CYP-regulated immunostimulants to activate macrophages and provides initial insight into the capacity of macrophages to regulate CYP activity induced by immunostimulants in fish.

Interleukin-1alpha and tumor necrosis factor alpha modulate cytochrome P450 activities in carp (Cyprinus carpio).

In mammals, it has been shown that the activation of host defense mechanisms down-regulates microsomal cytochrome P450 by the liberation of cytokines. We investigated the effect of interleukin-1alpha (IL1alpha) and tumor necrosis factoralpha (TNFalpha) on constitutive and 3-methylcholanthrene (3-MC)-induced biotransformation activities in carp. We have first measured the time course response of ethoxyresorufine O-decthylase (EROD) activity in liver, head kidney, and spleen 1, 2, 3, 5, and 7 days after intraperitoneal injection of a prototypical Cyp 1A inducer (3-MC). This activity was compared to the rate of 3-MC accumulation in all organs tested. A correlation between a diminution of EROD activity and an increase in 3-MC concentration in each organ was observed. We have also tested the effects of two inflammatory cytokines (IL1alpha and TNFalpha) on biotransformation activities. Intravenous injection of these compounds resulted in a marked depression of 3-MC-induced glutathione S-transferase activity in all organs tested and in 3-MC-increased cytochrome P450 content in the liver and head kidney. TNFalpha produced an increase in basal EROD activity in the liver and head kidney. Taken together, these results suggested that, as in mammals, the activation of host defense mechanisms regulates microsomal cytochrome P450 and related enzymes in fish.

The effects of 3-methylcholanthrene on lymphocyte proliferation in the common carp (Cyprinus carpio L.).

The sensitivity of lymphocyte proliferation as bioindicator of pollution stress was evaluated in the common carp (Cyrinus carpio L.). The time course response of peripheral blood leukocyte proliferation in response or not to mitogens was measured from 1 to 7 days after peritoneal injection of 3-methylcholantrene (3-MC), and compared to the time course response of a highly sensitive biomarker, induction of cytochrome P450. 3-Methylcholanthrene (40 mg kg(-1)) inhibited both B- and T-lymphocyte proliferation in response to lipopolysaccharide (LPS) and concanavalin A (Con A). Studies with alpha-naphtofiavone, suggest the lack of metabolic processes. 3-Methylcholanthrene alone strongly stimulated resting peripheral blood leukocytes (PBLs) proliferation. This effect was not transient. The induction of lymphocyte proliferation paralleled the increase in cytochrome P450 content in the liver. The specificity of polycyclic aromatic hydrocarbon (PAH)-induced lymphocyte proliferation suggests that this immune activity may be an early marker of exposure to PAHs in aquatic environments. The capacity of 3-MC to induce rapid lymphocyte proliferation may be related to PAH-induced rapid clonal expansion in mammals. These results strongly suggested that the underlying mechanism might be the same in both models. More studies are needed in fish to explain this phenomenon and may be helpful in understanding the occurrence of neoplastic epizootics in fish associated with PAH exposition.

3-Methylcholanthrene induces lymphocyte and phagocyte apoptosis in common carp (Cyprinus carpio L) in vitro.

Polycyclic aromatic hydrocarbons (PAH) are an important class of environmental pollutant that are known to be carcinogenic and immunotoxic. In mammals it was suggested that PAH compromise the immune system in part through the induction of programed cell death (apoptosis). In fish, no study has reported the importance of this physiological process in PAH-induced immunotoxicity. We have therefore investigated the capacity of 3-methylcholanthrene to induce lymphocyte and phagocyte apoptosis in carp. By three criteria (exposition of phosphatidylserine at the outer cell membrane, chromatin condensation and fragmentation, and decreased cell size) the data indicate that 3-methylcholanthrene (3-MC) treatment (from 20 to 200 microM) during 24 h produces apoptosis in both lymphocytes and phagocytes. In order to evaluate whether 3-MC induced apoptosis is related to the metabolic activation of 3-MC or 3-MC Ah-R binding, co-exposure experiments with 3-MC and alpha-naphtoflavone (alpha-NF), a compound that inhibits metabolic activation of 3-MC and 3-MC Ah-R binding were performed. While alpha-NF did not prevent 3-MC-induced apoptosis, the compound itself was found to be a strong inducer of apoptosis. There results might indicate that metabolic activation of 3-MC or 3-MC Ah-R binding is not causally linked to apoptosis. However, since 3-MC, alpha-NF and 3-MC + alpha-NF treatments produce the same sustained increase (3 h minimum) in intracellular calcium level, it is possible that this phenomenon is implicated in the induction of programmed cell death by these hydrocarbons.

3-methylcholanthrene inhibits lymphocyte proliferation and increases intracellular calcium levels in common carp (Cyprinus carpio L).

Polycyclic aromatic hydrocarbons (PAHs) are an important class of environmental pollutants that are known to be carcinogenic and immunotoxic. Many authors have focused on macrophage activities in fish exposed to PAHs. However, fewer studies have reported decrease in specific immunity in such fish. We investigated the intracellular mechanisms by which the 3-methylcholanthrene (3-MC) decreased lymphocyte proliferation in carp. T- and B-lymphocyte proliferation induced by Concanavalin A (Con A) and lipopolysaccharide (LPS) were inhibited by 3-MC (0.5-50 microM). 3-MC also produced a rapid and a sustained increase in intracellular calcium concentration ([Ca(2+)](i)) (2 h minimum). However, the cytochrome p450 1A and Ah receptor inhibitor, alpha-naphtoflavone (a-NF), also inhibited lymphocyte proliferation and did not reverse the effects of 3-MC. Moreover, since a-NF and 3-MC increased [Ca(2+)](i) and inhibited lymphocyte proliferation it was possible that calcium release played a role in 3-MC-inhibited lymphocyte proliferation. The rise in [Ca(2+)](i) induced by 3-MC was potentiated by the inhibitor of the endoplasmic reticulum calcium ATPases, thapsigargin. Treating cells with 3-MC decreased calcium mobilization caused by thapsigargin. These results suggest that 3-MC acts on the endoplasmic reticulum, perhaps directly on calcium ATPases, to increase intracellular calcium levels in carp leucocytes.

The effects of 3-methylcholanthrene on macrophage respiratory burst and biotransformation activities in the common carp (Cyprinus carpio L.).

The sensitivity of phagocytic cell function as a bioindicator of pollution stress by polycyclic aromatic hydrocarbons was evaluated in the common carp (Cyprinus carpio L). The time course response of the head-kidney macrophage respiratory burst was measured 1, 2, 3, 5 and 7 days after intraperitoneal injection of a prototypical Cyp 1A inducer (3-methylcholanthrene). This immune activity was compared to the rate of induction of total cytochrome P450, ethoxyresorufin O-deethylase activity (EROD) and glutathione S-transferase activity (GST) in the liver and head-kidney. 3-methylcholanthrene (40 mg kg(-1)) caused a rapid increase in the macrophage respiratory burst. This response was maximal at day 3 post exposure and coincided with maximum induction of cytochrome P450 and EROD activity in liver and head-kidney. Moreover, alpha-naphtoflavone, which functions as both an Ah receptor antagonist and an inhibitor of cytochrome P450 1A activity, reversed the 3-methylcholanthrene induction of immune and enzymatic parameters measured, suggesting metabolic processes. Taken together these results suggest that the induction of macrophage oxidative function may be an equally sensitive marker of exposure to polycyclic aromatic hydrocarbon as the induction of biotransformation activities and confirm that responses mediated by the Ah receptor are similar, if not identical, to those of mammals.

Lindane-induced macrophage activating factor (MAF) production by peripheral blood leukocytes (PBLs) of rainbow trout (Oncorhynchus mykiss): involvement of intracellular cAMP mobilization.

We studied the in vitro effects of the insecticide lindane (2.5-50 microM) on macrophage activating factor (MAF) production by the peripheral blood leukocytes (PBLs) in rainbow trout. The MAF production induced by the mitogens concanavalin A (ConA) and phorbol-12-myristate-13-acetate (PMA) was not modified by lindane pre-treatment. But lindane alone (2.5-25 microM) stimulated the secretion of MAF by PBLs. Intracellular calcium levels ([Ca2+]i) was measured over 6 min by spectrofluorimetry using Indo-1/AM as fluorescent probe. Lindane (25-100 microM) significantly increased the [Ca2+]i in PBLs, but had no effect on calcium at the dose that caused MAF secretion. Moreover, the effect of lindane on MAF production was potentiated by the inhibitor of phosphodiesterase, isobutylmethylxanthin (IBMX). Lindane also directly increased adenosine monophosphate cyclic (cAMP) in PBLs over the same concentration range that it stimulated MAF production by PBLs. Taken together, these results suggest that lindane increase MAF production by acting on intracellular cAMP concentrations. Moreover, the capacity of this insecticide to act on the [Ca2+]i or on the intracellular concentrations of cAMP according to the dose used could possibly explain its contradictory effects earlier observed on immunity.

3-Methylcholanthrene increases phorbol 12-myristate 13-acetate-induced respiratory burst activity and intracellular calcium levels in common carp (Cyprinus carpio L) macrophages.

Phagocytic cells play a key role in the fish immune system. They secrete reactive oxygen species (ROS) involved in their bactericidal activity. These cells are highly sensitive to pollution by polycyclic aromatic hydrocarbons and other organic pollutants. We have investigated the intracellular mechanisms by which 3-methylcholanthrene (3-MC) increased bactericidal activity of carp phagocytes. Macrophages isolated from head kidney (pronephros) and incubated 1 h with 3-MC enhanced their production of ROS when they were stimulated 1.25 h with phorbol 12-myristate 13-acetate (PMA), a direct activator of protein kinase C (PKC). 3-MC also produced a rapid and a sustained increase in [Ca(2+)](i) (2 h minimum). However, the cytochrome P450 1A and Ah receptor inhibitor, alpha-naphtoflavone (alpha-NF), inhibited the potentiation of PMA-induced ROS production, suggesting 3-MC metabolic activation. Moreover, alpha-NF increased [Ca(2+)](i) without macrophage ROS production, suggesting that some mechanism other than calcium release is playing a role in the stimulation of the macrophages by 3-MC. The rise in [Ca(2+)](i) induced by 3-MC was potentiated by the inhibitor of the endoplasmic reticulum calcium ATPases, thapsigargin. And treating the cells with 3-MC decreased the calcium mobilization caused by thapsigargin. These results suggest that 3-MC acts on the endoplasmic reticulum, perhaps directly on calcium ATPases, to increase intracellular calcium levels in carp phagocytes.

[Propofol anesthesia for ophthalmologic surgery in the elderly]. / Anesthésie au propofol en chirurgie ophtalmologique du sujet âgé.

Fifty patients more than 70 years old, ASA I and II, NYHA I and II, were anaesthetized by propofol for cataract or retinal detachment surgery. Induction was carried out by a propofol slow injection (0.5-1 mg.s-1) until loss eyelash reflex (mean dose 0.728 mg.kg-1) and completed by fentanyl 2 micrograms.kg-1 and vecuronium 0.08 mg.kg-1. After intubation, anaesthesia was maintained with nitrous oxide and continued infusion of propofol (mean dose 4.48 mg.kg-1.h-1) according to haemodynamic parameters. These were noted repeatedly and statistically analyzed. No significative differences were observed with younger patients undergoing identical surgical procedures. Haemodynamic effects were the same during cataract or retinal detachment surgery and in hypertensive treated patients vs non hypertensive ones. Recovery was as fast and good as in younger patients. It should be emphasized that propofol doses must be reduced in elderly patients so as to preserve a satisfactory haemodynamic stability. Reasons for increased sensitivity to propofol in elderly patients are briefly discussed.

[Anesthesia using propofol during surgery of strabismus in children. A comparison of two different protocols of induction and maintenance]. / Anesthésie au propofol lors de la chirurgie du strabisme chez l'enfant. Comparaison de deux protocoles différents d'induction et d'entretien.

The purpose of this study is an investigation of two protocols using propofol as induction and maintenance agent in 100 children scheduled for strabismus surgery (4-8 year, ASA I, NYHA I). Protocol I; Propofol 6 mg.kg-1 in 60 s with fentanyl 2 micrograms.kg-1 and vecuronium bromide 0.08 mg.kg-1 for induction, followed by propofol 11 mg.kg-1 for maintenance; Protocol II; Propofol 3 mg.kg-1 in 20 s with fentanyl 3 micrograms.kg-1 for induction, followed by propofol 12 mg.kg-1.h-1 for maintenance. It appears that the use of protocol I offers significant advantages compared with protocol II: a better quality of induction with a lesser incidence of pain during injection of propofol; a better quality of maintenance with very infrequent bradycardia from oculocardiac reflectivity; and a better recovery with a greatly reduced frequency of nausea and vomiting.