Effects of hypnosis on the relative parasympathetic tone assessed by ANI (Analgesia/Nociception Index) in healthy volunteers: a prospective observational study.

Hypnosis has shown an effect on the regulation of the autonomic nervous system by increasing parasympathetic activity. The Analgesia/Nociception Index (ANI) is derived from heart rate variability and represents the relative parasympathetic tone. We investigated the effects of hypnosis on ANI in healthy volunteers. Participants to the 2016 International Hypnosis congress, Saint Malo, France were recruited in this prospective observational study. After comfortable positioning of the subject in the sitting position (T0), the hypnotic trance was induced (T1) then conducted with suggestions of comfort (T2) before return to normal consciousness (T3). The ANI, heart rate (HR) and respiratory rate (RR) were recorded at the different time-points. Forty subjects were enrolled (31 women, 9 men). The mean ± SD ANI at T2 (84 ± 12) was significantly greater than at T0 (60 ± 10), T1 (62 ± 9) and T3 (59 ± 11). The median [25th-75th percentile] ANI values at T2 were significantly greater in women (90 [83-95]) than in men (74 [68-83]). There were no significant variations of HR during time. The median [25th-75th percentile] RR at T1 (16 [14-18] breaths/min) and T2 (14 [12-16] breaths/min) were significantly smaller than at T0 (18 [16-20] breaths/min) and T3 (18 [16-20] breaths/min). This study shows that hypnosis induces an increase in the relative parasympathetic tone assessed by ANI in healthy volunteers, with greater ANI values observed in women. These results suggest that ANI monitoring may provide an objective tool for the measurement of the intensity of the hypnotic process, although this should be confirmed by further studies.

Insights into the mechanism of electrocatalysis of the oxygen reduction reaction by a porphyrinic metal organic framework.

Metal Organic Frameworks (MOFs) have been recently proposed as promising electrocatalysts, yet the exact nature of the mechanisms in play has not been addressed in depth. By comparing the electrocatalytic activity of a MOF for the oxygen reduction reaction (ORR) and the corresponding molecular building units through electrochemical techniques, here, we investigate the nature of the catalytic sites, their redox states and the electron transfer pathways.

Seasonal monitoring of blue mussel (Mytilus spp.) populations in a harbor area: A focus on responses to environmental factors and chronic contamination.

Coastal waters corresponding to macrotidal systems are among the most variable marine biotopes. Sessile animals as bivalve mollusks may however be found forming intertidal beds at high densities, as allowed by full adaptation to local conditions. A better knowledge of adaptive responses to environmental factors is required to foresee possible adverse effects of global change. At the sub-cellular level, transcriptional responses are among the earliest signals of environmental disturbances and they can reveal subtle and meaningful changes in organism exposed to stress. Three blue mussel (Mytilus spp.) populations inhabiting the Bay of Brest (France) in sites exposed to different levels of chronic pollution, from low to moderate, were surveyed upon a seasonal schedule, with special attention to the reproductive cycle. Major seawater parameters were monitored over a full-year in the framework of the S!RANO project, based on an automatic high frequency acquisition system installed aboard a ship of opportunity. The health status of mussels has been assessed by measuring a condition index and gametogenesis has been followed by histology. Selected biological responses to environmental stress were detected using a multimarker approach including expression of genes involved in chemical stress response and energetic metabolism, and cellular immune parameters. Environmental parameters showed deep seasonal variations which differed among sites. Most biological responses followed a seasonal pattern. Late winter and spring corresponded to an active reproduction period in the Bay of Brest. Earlier spawning was observed in harbor areas compared to the oceanic site and an altered physiological state was assumed in commercial harbor mussels during the reproductive period, suggesting that their health is compromised at this time of year. However, no signs of severe chemical stress were detected in both harbor mussel populations, which could reflect adaptive responses to adverse environmental conditions.

The NLRP3 inflammasome is activated by nanoparticles through ATP, ADP and adenosine.

The NLR pyrin domain containing 3 (NLRP3) inflammasome is a major component of the innate immune system, but its mechanism of activation by a wide range of molecules remains largely unknown. Widely used nano-sized inorganic metal oxides such as silica dioxide (nano-SiO2) and titanium dioxide (nano-TiO2) activate the NLRP3 inflammasome in macrophages similarly to silica or asbestos micro-sized particles. By investigating towards the molecular mechanisms of inflammasome activation in response to nanoparticles, we show here that active adenosine triphosphate (ATP) release and subsequent ATP, adenosine diphosphate (ADP) and adenosine receptor signalling are required for inflammasome activation. Nano-SiO2 or nano-TiO2 caused a significant increase in P2Y1, P2Y2, A2A and/or A2B receptor expression, whereas the P2X7 receptor was downregulated. Interestingly, IL-1ß secretion in response to nanoparticles is increased by enhanced ATP and ADP hydrolysis, whereas it is decreased by adenosine degradation or selective A2A or A2B receptor inhibition. Downstream of these receptors, our results show that nanoparticles activate the NLRP3 inflammasome via activation of PLC-InsP3 and/or inhibition of adenylate cyclase (ADCY)-cAMP pathways. Finally, a high dose of adenosine triggers inflammasome activation and IL-1ß secretion through adenosine cellular uptake by nucleotide transporters and by its subsequent transformation in ATP by adenosine kinase. In summary, we show for the first time that extracellular adenosine activates the NLRP3 inflammasome by two ways: by interacting with adenosine receptors at nanomolar/micromolar concentrations and through cellular uptake by equilibrative nucleoside transporters at millimolar concentrations. These findings provide new molecular insights on the mechanisms of NLRP3 inflammasome activation and new therapeutic strategies to control inflammation.

ATP release and purinergic signaling: a common pathway for particle-mediated inflammasome activation.

Deposition of uric acid crystals in joints causes the acute and chronic inflammatory disease known as gout and prolonged airway exposure to silica crystals leads to the development of silicosis, an irreversible fibrotic pulmonary disease. Aluminum salt (Alum) crystals are frequently used as vaccine adjuvant. The mechanisms by which crystals activate innate immunity through the Nlrp3 inflammasome are not well understood. Here, we show that uric acid, silica and Alum crystals trigger the extracellular delivery of endogenous ATP, which just precedes the secretion of mature interleukin-1ß (IL-1ß) by macrophages, both events depending on purinergic receptors and connexin/pannexin channels. Interestingly, not only ATP but also ADP and UTP are involved in IL-1ß production upon these Nlrp3 inflammasome activators through multiple purinergic receptor signaling. These findings support a pivotal role for nucleotides as danger signals and provide a new molecular mechanism to explain how chemically and structurally diverse stimuli can activate the Nlrp3 inflammasome.

NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant.

BACKGROUND: Inflammasome activation with the production of IL-1ß received substantial attention recently in inflammatory diseases. However, the role of inflammasome in the pathogenesis of asthma is not clear. Using an adjuvant-free model of allergic lung inflammation induced by ovalbumin (OVA), we investigated the role of NLRP3 inflammasome and related it to IL-1R1 signaling pathway. METHODS: Allergic lung inflammation induced by OVA was evaluated in vivo in mice deficient in NLRP3 inflammasome, IL-1R1, IL-1ß or IL-1α. Eosinophil recruitment, Th2 cytokine, and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates, and mediastinal lymph node cells ex vivo. RESULTS: Allergic airway inflammation depends on NLRP3 inflammasome activation. Dendritic cell recruitment into lymph nodes, Th2 lymphocyte activation in the lung and secretion of Th2 cytokines and chemokines are reduced in the absence of NLRP3. Absence of NLRP3 and IL-1ß is associated with reduced expression of other proinflammatory cytokines such as IL-5, IL-13, IL-33, and thymic stromal lymphopoietin. Furthermore, the critical role of IL-1R1 signaling in allergic inflammation is confirmed in IL-1R1-, IL-1ß-, and IL-1α-deficient mice. CONCLUSION: NLRP3 inflammasome activation leading to IL-1 production is critical for the induction of a Th2 inflammatory allergic response.

[Ambulatory Essure implant placement sterilization procedure for women: prospective study comparing general anesthesia versus hypnosis combined with sedation]. / Étude prospective comparant l'hypnosédation et l'anesthésie générale pour la pose de dispositif de stérilisation intratubaire en ambulatoire.

OBJECTIVE: implant placement Essure, sterilization procedure for women, were performed under hypnosedation (HYP) and compared to the operative anxiety and analgesia of 12 patients operated-on under general anesthesia (GA). STUDY DESIGN: prospective and comparative group study. PATIENTS AND METHODS: two groups of twelve patients were matched and compared based on the choice of anesthetic technique: hypnotics (HYP) with possible additional sedation by propofol and remifentanil or GA involving propofol, sevoflurane and remifentanil. The assessment of anxiety and pain based on a visual analogy scale (0-10) and use of analgesics were studied in the recovery room and at discharge of hospital. The statistical analysis relies on nonparametric tests for paired data (Wilcoxon test). RESULTS: all patients were operated. The two groups are statistically comparable. The preoperative anxiety before premedication is lower in the HYP group (p<0.05). No conversion to general anaesthesia is necessary in the HYP group, but five patients were using sedatives drugs but doses are very low compared to general anaesthesia. The analgesic consumption was equivalent in both groups. CONCLUSION: we conclude that hypnosedation is a valuable alternative to traditional anesthetic techniques for ambulatory Essure implant. The use of hypnotic tool is an interesting alternative for the management of patients during invasive medical procedures or surgical, providing psychological benefits to the patient.

Successful but prolonged resuscitation after local anesthetic-induced cardiac arrest: is clonidine effective?

Local anesthetics when injected intravascularly result in serious cardiac complications including therapy-resistant cardiac arrest. We report a case of cardiac arrest after lumbar plexus block using a combination of 0.5% bupivacaine and 2% lidocaine with epinephrine (1:200.000). Resuscitation was performed by a combination of chest compression, repeated external countershocks and i.v.epinephrine. Clonidine had poor effect. The whole resuscitation required 90 minutes. The patient was discharged four days later without any sequelae. Blood sampling at 10 minutes showed a concentration of 2.02 mg/l lidocaine and 0.87 mg/l bupivacaine. Prolonged resuscitation is necessary in local anesthetic-induced cardiac arrest.

[Psoas compartment block with general anaesthesia: descriptive study of 93 cases]. / Bloc du plexus lombaire par voie postérieure réalisé sous anesthésie générale: étude descriptive de 93 cas.

OBJECTIVES: During many years the approach to the lumbar plexus has been the anterior paravascular technique described as a "3-1" block by Winnie. The posterior approach results in a complete block of the principal nerves of the lumbar plexus. The goal of the study was to evaluate the performance of the psoas compartment block with general anaesthesia. STUDY DESIGN: Prospective, descriptive, non randomized study. PATIENTS AND METHODS: Ninety-three patients scheduled for hip surgery were studied after informed consent. Demographic data, technical aspects of the puncture, complications, and intra- and postoperative analgesics were recorded. RESULTS: The block was performed by resident alone, senior alone, both in respectively 44%, 45, and 11% of cases. The mean duration of the procedure was 6+/-3 min for the residents, 5+/-2 min for the seniors, and 9+/-4 min for both. The transverse process was reach in 72% of cases during the first approach, after reorientation of the needle in the others cases, except 3 failures of attempt. The lumbar plexus was assessed within 60-90 mm of depth, with a median of 75 mm. The motor response was mainly a femoral response; the minimal intensity of stimulation was ranged between 0.3 and 1 mA, with a median of 0.6 mA. The duration of analgesic block was 16.5+/-4.5 hours, with a median of 18 hours. The morphine use during the first postoperative 24 hours was 8+/-8 mg, with a median of 5.6 mg. No neurologic complication was recorded at discharge from the hospital. CONCLUSION: The psoas compartment block with general anaesthesia have shown it feasibility and efficiency on intra- and postoperative analgesia during hip surgery.

Chemistry-structure-simulation or chemistry-simulation-structure sequences? The case of MIL-34, a new porous aluminophosphate.

A new aluminophosphate, MIL-34, is investigated from its as-synthesized structure to its calcined microporous form. Single-crystal X-ray diffraction measurements on the as-synthesized MIL-34 (Al(4)(PO(4))(4)OH x C(4)H(10)N, space group P-1, a = 8.701(3) A, b = 9.210(3) A, c = 12.385(3) A, alpha = 111.11(2) degrees, beta = 101.42(2) degrees, gamma = 102.08(2) degrees, V = 863.8(4) A(3), Z = 2, R = 3.8%) reveal a 3-D open framework where Al atoms are in both tetrahedral and trigonal bipyramidal coordinations. It contains a 2-D pore system defined by eight rings where channels along [100] cross channels running along [010] and [110]. CBuA molecules are trapped at their intersection. (27)Al, (31)P, and (1)H MAS NMR spectroscopies corroborate these structural features. Calcination treatments of a powder sample of the as-synthesized MIL-34 indicate its transformation into the related template-free structure that is stable up to 1000 degrees C. Lattice energy minimizations are then used in order to anticipate the crystal structure of the calcined MIL-34, starting with the knowledge of the as-synthesized structure exclusively. Energy minimizations predict a new regular zeotype structure (AlPO(4), space group P-1, a = 8.706 A, b = 8.749 A, c = 12.768 A, alpha = 111.17 degrees, beta = 97.70 degrees, gamma = 105.14 degrees, V = 846.75 A(3), Z = 2) together with a thermodynamic stability similar to that of existing zeotype AlPOs. Excellent agreement is observed between the diffraction pattern calculated from the predicted calcined MIL-34 and the experimental X-ray powder diffraction pattern of the calcined sample. Finally, the atomic coordinates and cell parameters of the calcined MIL-34 predicted from the simulations are used to perform the Rietveld refinement of the calcined sample powder pattern, further corroborated by (27)Al and (31)P NMR measurements. This unique combination of experiment and simulation approaches is an interesting and innovative strategy in materials sciences, where simulations articulate the prediction of a possible template-free framework from its as-synthesized templated form. This is especially valuable when straightforward characterizations of the solid of interest with conventional techniques are not easy to carry out.

Hydrothermal synthesis and ab initio structural resolution from X-ray powder diffraction of a new open framework Cu(II) carboxyethylphosphonate: Na[Cu(O3P-(CH2)2-CO2)].

Na[Cu(O3P-(CH2)2-CO2)], or MIL-39 (for Material of Institut Lavoisier), was synthesized hydrothermally at 443 K for 72 h under autogenous pressure. Its three-dimensional open structure was determined from X-ray powder diffraction. MIL-39 is monoclinic, it crystallizes in the space group P2(1)/m, (No. 11) with the following cell parameters at 293 K: a = 8.808(1) A, b = 6.4149(8) A, c = 5.3418(8) A, beta = 105.75(1) degrees, Z = 2. Its framework contains double rows built from isolated distorted CuO5 square pyramids linked by PO3C tetrahedral groups from (O3P-(CH2)2-CO2)3- organic moieties. At the other end of these latter moieties, the carboxylate group links two different Cu polyhedra of two neighboring chains. These connections define two types of channels along [010].

Tetraaquabis(3,5-dicarboxybenzoato-O)cobalt(II)

The hydrothermal reaction of cobalt(II) chloride with trimesate (3, 5-dicarboxybenzoate) ions in aqueous solution gives the novel title complex, [Co(C(9)H(5)O(6))(2)(H(2)O)(4)]. The Co(II) ion lies on an inversion centre and is octahedrally coordinated to two trimesate anions and four water molecules. Hydrogen bonds ensure the three-dimensional architecture of the structure.

Influence of somatostatin on acute pancreatitis in rats.

OBJECTIVE: To assess the effect of two regimens of somatostatin on the morbidity and short term outcome of acute pancreatitis in rats. DESIGN: Randomised laboratory study. SETTING: Teaching hospital, France. ANIMALS: 24 male Wistar rats. INTERVENTIONS: Rats were randomised to 3 groups of 8, 2 of which were given somatostatin (one 25 microg/kg/hour by continuous infusion and one as a bolus injection of 5 microg before the infusion of 25 microg/kg/hour); the third (control) group was given 0.9% of saline 25 microg/kg/hour. Acute pancreatitis was induced by ligating the pancreatic duct at the junction with the duodenum. MAIN OUTCOME MEASURES: Serum amylase and lipase activities at 2 and 4 hours, and histological changes after 4 hours, at which time the animals were killed and the pancreas removed. RESULTS: Amylase and lipase activities were significantly lower in the somatostatin groups than in the control group throughout the experiment (p < 0.001). They were slightly but not significantly lower in the bolus group than the infusion group. The degree of necrosis and the extent of inflammatory infiltration were significantly less in the somatostatin groups (p < 0.008). CONCLUSION: Somatostatin has an early favourable effect on the course of experimentally induced pancreatitis in rats.

Antiinflammatory properties of cetirizine in a human contact dermatitis model. Clinical evaluation of patch tests is not hampered by antihistamines.

The aim of this double-blind, placebo-controlled, randomized, cross-over pilot study was to assess the antiinflammatory properties of cetirizine. A group of 27 patients with a positive patch test to an allergen consecutively received cetirizine 10 mg o.d. or placebo during a 14-day period, respectively. At day 11 of each period, patch testing was performed with the allergen. The image analysis showed a skin reaction significantly reduced under cetirizine (p = 0.03), but the clinical recording and the standardized chromatometry did not show any difference between groups. In the cross-over analysis the results of image analysis were influenced by the period, but this effect disappeared after adjustment of the ambient temperature during the 3 days of the test. These results demonstrate that cetirizine has an impact on the inflammatory process in a clinical model of cell-mediated allergic reaction, although this effect is only detected with a very sensitive technique. They also show that it is useless to stop antihistamines before patch testing, since clinical evaluation of tests is not hampered by a potent antihistamine. Additionally this study suggests that ambient temperature has an influence on the results of tests.

[Effects of co-administration of an antidepressant and an anxiolytic drug in the "learned helplessness" paradigm: importance of hydroxyzine]. / Effets d'une coadministration d'antidépresseur et d'anxiolytique dans le paradigme de "learned-helplessness": intérêt de l'hydroxyzine.

Whereas benzodiazepines are routinely coadministered with tricyclic antidepressants, in patients undergoing treatment for depressive disorders, little information is known about the combination of benzodiazepines with other antidepressants such as specific serotonin reuptake inhibitors (SSRI's), and combination with other anxiolytic drugs. On the other hand, it is known that benzodiazepines decrease the serotoninergic transmission. The present study was undertaken to evaluate the effect of concomittant administration of anxiolytic drugs such as benzodiazepines (diazepam, lorazepam) or diphenylmethane derivative (hydroxyzine) with specific serotonin reuptake inhibitors, (fluvoxamine, fluoxetine, indalpine) on the ability of antidepressant drugs to reverse helpless behavior in this test. Our results show that: daily injection of diazepam (0.25-2 mg/kg), lorazepam (0.06-0.25 mg/kg) or hydroxyzine (8.32 mg/kg) failed to reverse the behavioral deficit in rat. In contrast fluvoxamine: 4 mg/kg/day; fluoxetine: 4 mg/kg/day; indalpine: 1 mg/kg/day significantly reverse the helpless behavior in this test; the reversal of helpless behavior by fluvoxamine or indalpine was dose-dependently antagonized by daily coadministration of diazepam or lorazepam; in contrast, the reversal of helpless behavior by fluvoxamine or fluoxetine was not modified by daily coadministration of hydroxyzine (8 mg/kg). In conclusion, it may be suggested that combined benzodiazepine-specific serotonin reuptake inhibitors, should be avoided. We suggest that anxiolytic drugs such as hydroxyzine might be better in coadministration with antidepressants, particularly with specific serotonin reuptake inhibitors.

[Modification of cognitive functions by 2 anxiolytic treatments in patients suffering from generalized anxiety]. / Retentissement sur les fonctions cognitives de deux traitements anxiolytiques chez des patients souffrant d'anxiété généralisée.

The aim of this randomized, double-blind, multicentric study was to assess and compare cognitive impairment in patients treated with either lorazepam or hydroxyzine, for generalized anxiety. Only non depressed patients were selected according to MADRS criteria. The cognitive assessment was performed with the BEC 96 rating scale, the intensity of anxiety symptoms was evaluated through the Hamilton-anxiety and Covi scales. The level of relation, mood and sedation was assessed for each item with a visual analog scale (VAS). The patient's and investigator's opinion on the global efficiency of the treatment were also evaluated on VAS. After an 8-day wash-out period under placebo, the treatment was given in a double-blind way for 28 days: either hydroxyzine 25 mg at a daily dosage of 100 mg t.i.d. (25 mg - 25 mg - 50 mg), or lorazepam 1 mg at a daily dosage of 4 mg t.i.d. (1 mg - 1 mg - 2 mg). The results were as follows: after the 28-day treatment period, patients showed at the BEC 96 a cognitive improvement in both groups, but the improvement in the hydroxyzine group was significantly higher. Furthermore, the improvement appeared more quickly in the hydroxyzine group. The Hamilton-anxiety and Covi scales showed an improvement in the anxiety level in both groups with no significant difference. The visual analog scales assessing relation, mood and sedation improved in both groups as well as the patient's and investigator's opinion. The five assessments all showed a significant by higher improvement in the hydroxyzine group.(ABSTRACT TRUNCATED AT 250 WORDS)

Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs?

The in vitro activity of 13 drugs against 552 clinical isolates of atypical mycobacteria representing 12 species was performed in 7H11 agar medium at the National Reference Laboratory for Mycobacteria, using the 1% proportion method. All the species tested were resistant to isoniazid and pyrazinamide. In general, clofazimine and D-cycloserine showed the widest spectrum of activity except in the case of Mycobactrium fortuitum and M. chelonei which were resistant to both drugs, and the M. szulgai and M. terrae complex which was resistant to D-cycloserine. The next broad-spectrum drug was ethionamide, followed by ansamycin, rifampin, capreomycin, kanamycin, streptomycin and ethambutol. Among the fluoroquinolones, both ciprofloxacin and ofloxacin were active against M. xenopi, M. gordonae and M. fortuitum whereas M. kansasii and M. gastri were sensitive to ofloxacin only. When the species were listed in respect of the number of drugs to which they were susceptible (less than 10% of resistant strains), they were classified as follows; 7/13 drugs for M. kansasii, M. gastri and M. xenopi; 6/13 for M. gordonae; 5/13 for M. marinum; 3/13 for M. szulgai; 2/13 for M. fortuitum; 1/13 for the M. avium, M. scrofulaceum, M. simiae, and M. terrae complex, and none of the 13 in the case of M. chelonei. These results are discussed in relation to the multiple drug resistance of atypical mycobacteria. We conclude that the critical concentrations of drugs established for M. tuberculosis are not appropriate for atypical mycobacteria.

[Does the hydrolysis of proteins change the acceptability and the digestive tolerance of milk for infants? The results of a comparative and randomized prospective study]. / L'hydrolyse des protéines modifie-t-elle l'acceptabilité et la tolérance digestive d'un lait pour nourrissons? Résultats d'une étude prospective comparative et randomisée.

A prospective randomized study of growth and digestive tolerance in a cohort of 60 healthy infants with no history for allergic disease is reported. A milk-based formula and a formula of identical composition whose proteins had undergone hydrolysis were fed successively to the study infants according to a crossover design, for eight weeks. Intake, weight gain and length gain were comparable and satisfactory with both diets. With the hydrolyzed protein formula, stools were greener in color and significantly more numerous, although both parameters remained within normal limits. The most noteworthy result was the significantly greater rate of regurgitations in the group given the hydrolyzed protein formula, i.e., 26% versus 8% in the group fed a conventional modified milk formula. These results show that use of partial protein hydrolysate formulas is associated with minor digestive adverse effects.