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The present study uses large-eddy simulations (LES) to identify the underlying mechanism that governs the ignition and stabilization mechanisms of ECN Spray A flame for different injection pressures (P inj) and ambient temperatures (T am). Two P inj of 50 MPa and 150 MPa, as well as two T am of 750 K and 900 K are considered. The numerical model is validated against the experimental fuel penetration, radial mixture fraction distribution, ignition delay time, and lift-off length. The combustion characteristics of all four spray flames are well predicted, with a maximum relative difference of 15% to the measurements. At 900 K, high-temperature ignition (HTI) occurs in the fuel-rich mixture at the spray head of the high P inj spray flame, but at the spray periphery of the low P inj spray flame. This is due to the low P inj case having fuel-richer mixture in the inner spray region. Nonetheless, the spray flames at both P inj exhibit double-flame structure. At 750 K, HTI occurs at the fuel-rich and fuel-lean regions for spray flames with P inj = 50 MPa and 150 MPa, respectively. Reducing the P inj leads to a lower injection velocity, less turbulent fluctuation, slower mixing, and hence the occurrence of HTI at the fuel-rich mixtures. The spray flame in the low P inj case at 750 K exhibits a triple-flame structure at the lift-off position, while the high P inj case exhibits a lean premixed reaction zone. This difference is attributed to the distribution of fuel-rich mixtures. Despite differences in the flame structures, auto-ignition process plays a key role to stabilize the lift-off position for all four spray flames. The auto-ignition process is also found to be dependent on the cool-flame products upstream of the lift-off position. In particular for the low T am cases, the heat transfer effect from the main flame to the fuel-rich regions is suggested to also contribute to the flame stabilization mechanisms. [ABSTRACT FROM AUTHOR]

The Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care. [ABSTRACT FROM AUTHOR]

In the present study, large-eddy simulations (LES) are used to identify the underlying mechanism that governs the ignition phenomena of spray flames from different nozzle diameters when the ambient temperature (T am) varies. Two nozzle sizes of 90µm and 186µm are chosen. They correspond to the nozzle sizes used by Spray A and Spray D, respectively, in the Engine Combustion Network. LES studies of both nozzles are performed at three T am of 800K, 900K, and 1000K. The numerical models are validated using the experimental liquid and vapor penetration, mixture fraction (Z) distribution, as well as ignition delay time (IDT). The ignition characteristics of both Spray A and Spray D are well predicted, with a maximum relative difference of 14% as compared to the experiments. The simulations also predict the annular ignition sites for Spray D at T am ⩾ 900K, which is consistent with the experimental observation. It is found that the mixture with Z ⩽ 0.2 at the spray periphery is more favorable for ignition to occur than the overly fuel-rich mixture of Z > 0.2 formed in the core of spray. This leads to the annular ignition sites at higher T am. Significantly longer IDT for Spray D is obtained at T am of 800K due to higher scalar dissipation rates (χ) during high temperature (HT) ignition. The maximum χ during HT ignition for Spray D is larger than that in Spray A by approximately a factor of 5. In contrast, at T am = 1000 K, the χ values are similar between Spray A and Spray D. This elucidates the increase in the difference of IDT between Spray D and Spray A as T am decreases. This may explain the contradicting findings on the effects of nozzle diameters on IDT from literature. [ABSTRACT FROM AUTHOR]

This document is a summary of the French Intergroup guidelines regarding the management of gastrointestinal stromal tumours (GISTs) updated in December 2018. This collaborative work summarizes clinical practice recommendations (guidelines) on the management of GISTs. It is based on recent literature review, ESMO recommendations and expert opinions. The diagnosis of GIST is based on histological examination and immunohistochemistry with markers KIT and DOG-1. Each case must be discussed within a multidisciplinary team. Complete surgical resection tumour, avoiding peroperative perforation, is the potentially curative treatment of localized GISTs. The estimation of the recurrence risk is essential, or adjuvant treatment,and follow-up adaptation. Genotyping (KIT and PDGFRA) of all but very low-risk GISTs is recommended. The nature of mutation has a prognostic value and predictive influence on drug efficacy. Imatinib, a tyrosine-kinase inhibitor, is the standard adjuvant treatment after R0 resection of a GIST with a high risk of recurrence, and the first line therapy for advanced GISTs. Suninitib and regorafenib are respectively the second- and third-line standard treatments for advanced GISTs. Guidelines for management of GISTs are continuously evolving and need to be regularly updated. This constant progress is made possible through clinical and translational research. [ABSTRACT FROM AUTHOR]

Highlights from the article: Retroperitoneal sarcomas are rare tumors that affect approximately 600 people every year in metropolitan France. The psoas muscle fascia, which constitutes the posterior limit of the compartment and must be removed, is incised and dissection is continued medially to the aortic bifurcation along the upper edge of the external and common iliac vessels, which is the distal limit of the compartment. The inferior vena cava (IVC) for right-sided tumors or the aorta for left-sided tumors, is progressively freed from the tumor, from the bottom upwards, at the same time incising the medial insertion of the psoas fascia.

Myxoid liposarcoma (MLS) is a rare mesenchymal tumor that constitutes 10-20% of all liposarcomas. MLS is a translocation-related sarcoma (TRS) related to the chromosomal translocation t(12:16) (q13:p11), producing the FUS-CHOP oncoprotein that constitutes one of the main targets of trabectedin in MLS patients. It is known to be chemosensitive namely to trabectedin in contrast to other soft tissue sarcomas. The efficacy of this agent in MLS have been demonstrated in different settings including treatment-naïve and pre-treated patients with both locally advanced and metastatic disease. However, the benefits of trabectedin in MLS are shadowed by the limited activity of this drug in other subtypes of sarcomas that are enrolled within the same trials. This prompted us to screen the medical literature for clinical data that evaluates the efficacy and safety of trabectedin in MLS. In this review, we will summarize the available evidence for the applicability of trabectedin in MLS. [ABSTRACT FROM AUTHOR]

The present numerical study aims to assess the performance of an Eulerian Stochastic Field (ESF) model in simulating spray flames produced by three fuel injectors with different nozzle diameters of 100 µm, 180 µm and 363 µm. A comparison to the measurements shows that although the simulated ignition delay times are consistently overestimated, the relative differences remain below 28%. Furthermore, the change of the averaged pressure rise with respect to the variation of nozzle diameter is captured by the model. The simulated flame lift-off lengths also agree with the measurements, with a maximum relative difference of 13%. The spray flame produced by a larger nozzle diameter has a fuel-richer premixed core region despite the longer lift-of length, indicating that the higher fueling rate used with the larger nozzle diameter is a more dominating factor than the lift-off length is in influencing the air entrainment into the upstream of the spray flames. In addition, the simulated normalised flame lengths are found to decrease when the nozzle diameters increase. These predictions are in good qualitative agreement with the experimental observation. This work proves that the ESF model can serve as an important tool for the simulation of spray flames in marine diesel engines, where fuel injectors with different nozzle diameters are applied for pilot and main injections. [ABSTRACT FROM AUTHOR]

Background Extra-pleural and extra-meningeal solitary fibrous tumour (SFT) is a rare sarcoma histotype curable with surgery in the majority of patients. The behaviour of these tumours ranges from indolent/very low grade to malignant/high grade but it is still not possible to accurately predict prognosis after surgery. We have investigated a multi-centre series to stratify the risk of recurrence to patients with SFTs. Methods We retrospectively analysed the data from 243 patients who underwent surgery (2002–2011) at four sarcoma referral centres. Results Upon univariate analysis, hypercellularity, atypia, necrosis, high mitotic rate (ie >4 mitoses/10 HPF) were associated with both disease-free and overall survival. Surgical margins were a significant prognostic factor for disease-free (P = 0.007) but not for overall survival. Unexpectedly, larger tumour size was associated with a better prognosis (P = 0.038) and fewer recurrences (P = 0.024). Upon multivariable analysis, high mitotic rate (hazard ratio, HR = 2.85, P = 0.002), cellular atypia (HR = 1.62, P = 0.015) and hypercellularity (HR = 1.82, P = 0.031) were significantly associated with recurrences. A SFT recurrence score has been provided to stratify risk of recurrence. Conclusion This study provides a prognostic model to stratify risk of recurrence in patients with resectable SFTs. This allows clinician to decide on an optimal follow-up strategy and to select patients that may benefit from adjuvant treatments. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The prognosis of peritoneal carcinomatosis (PC) is highly dependent on the extent of the PC. This extent is calculated by the peritoneal cancer index (PCI). In the future, the indications for complete cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) should be partially based on the PCI. This raises the question of the concordance between the PCI scores calculated by different surgeons, and a possible variation before and after CRS. Objective: To analyze variations in the PCI score between surgeons and according to when it is determined (before and after surgery). Patients and methods: Prospective recording of the PCI score independently calculated by senior and junior surgeons, before CRS (when the surgeon decided to perform this procedure), and after CRS, in 75 consecutive patients. A concordance analysis was conducted. Results: The origins of the PC were colorectal (n = 38), pseudomyxoma (n = 22), mesothelioma (n = 8) and miscellaneous lesions (n = 7). Concordance between the PCI score was very high (close to 90%) among the senior surgeons and junior surgeons before and after CRS. After CRS, the mean PCI score increased by 1.75 (IC-95%: 2.09–1.41). This high concordance was similar whatever the level of the PCI score and whatever the origin of the tumor. Conclusion: The PCI is a reliable tool for measuring the extent of PC. It is easy to use and inter-surgeon concordance is high. It increases by approximately 2 before and after CRS. [Copyright &y& Elsevier]

Abstract: Activation of Rho kinase (ROCK) has been shown to play a role in neuronal regeneration and development of posttraumatic neuropathic pain. The ROCK inhibitor Fasudil, used clinically for the treatment of vasospasm, was used to investigate the analgesic profile of a ROCK inhibitor. Fasudil was evaluated in different preclinical models of neuropathic, osteoarthritic (OA), and inflammatory pain as well as capsaicin-induced acute pain and secondary mechanical hypersensitivity. In addition, Fasudil was tested in in vivo electrophysiology to determine the mechanism by which Fasudil produces analgesia. Fasudil at the highest dose tested (30 mg/kg) significantly attenuated mechanical allodynia in spinal-nerve ligation (SNL; 77%), chronic constriction injury (CCI; 53%), capsaicin-induced secondary mechanical hypersensitivity (63%), sodium iodoacetate-induced OA pain (88%), and capsaicin-induced acute flinching behaviors (56%). However, Fasudil (at 30 mg/kg) failed to attenuate or had only modest effects on inflammatory thermal hyperalgesia following carrageenan injection and mechanical allodynia following Complete Freund''s Adjuvant (CFA) injection. Fasudil produced ED50 of 10.8 mg/kg in the SNL, and 5.7 mg/kg in the OA pain models. The ED50 and 95% CI could not be obtained in the other models. Furthermore, administration of Fasudil (10 mg/kg, iv) significantly reduced both spontaneous and evoked firing of wide dynamic range (WDR) neurons in SNL, but not sham rats. Finally, Fasudil significantly decreased exploratory behaviors at 30 mg/kg. These results suggest that the acute administration of a ROCK inhibitor produces efficacy in both neuropathic and nociceptive pain states at doses devoid of locomotor side effects, with specific effects on WDR neurons. Perspective: In this article, the potential analgesic effects of Fasudil in a range of preclinical pain models were assessed. Fasudil was shown to have efficacy in neuropathic and nociceptive pain models. These findings may help identify new therapeutic treatments for pain in the clinic. [Copyright &y& Elsevier]

Abstract: Peripheral nerve injury leads to neuropathic pain, but the underlying mechanisms are not clear. The TRPV1 channel expressed by nociceptors is one receptor for noxious heat and inflammatory molecules. Lumbar 4 (L4) spinal nerve ligation (SNL) in mice induced persistent heat hyperalgesia 4 to 10 days after injury. The heat hypersensitivity was completely reversed by the TRPV1 antagonist A-425619. Furthermore, DRG neurons were isolated from the injured L4 ganglia or adjacent L3 ganglia 4 to 10 days after L4 SNL. Whole-cell patch-clamp recordings were performed and heat stimuli (22°C to 50°C/3 s) were applied to the soma. Neurons were classified by soma size and isolectin-B4 (IB4) binding. Among directly injured L4 neurons, SNL increased the percentage of small-diameter IB4-positive neurons that were heat-sensitive from 13% (naive controls) to 56% and conversely decreased the proportion of small IB4-negative neurons that were heat-sensitive from 66% (naive controls) to 34%. There was no change in IB4 binding in neurons from the injured ganglia. Surprisingly, in neurons from the adjacent L3 ganglia, SNL had no effect on the heat responsiveness of either IB4-positive or negative small neurons. Also, SNL had no effect on heat responses in medium-large–diameter neurons from either the injured or adjacent ganglia. Perspective: TRPV1 function is upregulated in IB4-positive sensory neurons, and TRPV1 is responsible for the behavioral heat hypersensitivity in the spinal nerve ligation model. Because IB4-positive neurons may contribute to the emotional perception of pain, TRPV1 antagonists, targeting both sensory and affective pain components, could have broad analgesic effects. [Copyright &y& Elsevier]

Abstract: Background: Combining complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a new approach allowing curatively intended treatment of multiple malignant peritoneal tumour seedings. This aggressive treatment is frequently followed by a complicated or an unusual postoperative course, that has yet to be described. Aim: To describe the clinical and biological post-therapeutic course of patients treated with CCRS plus HIPEC, who were considered uncomplicated cases, and were discharged from hospital before the 15th postoperative day. Patients and methods: Thirty-two patients were retrospectively selected on these criteria among 232 treated patients, most of whom had received intraperitoneal high-dose oxaliplatin and intravenous 5-fluorouracil. The daily postoperative clinical and biological parameters are presented in graphs using boxplots. Results: Hyperthermia at 38°C was the rule during the first postoperative week. The daily flow rate of the abdominal drains decreased progressively from 500ml to 50ml from day 1 to day 7. The flow rate of the nasogastric tube was high and close to 1000ml/24h until day 6. Resumption of digestive transit occurred between day 4 and day 6; it was always a diarrheic transit until day 12. Severe hypophosphoremia was observed at day 2 and day 3. White blood cells gradually decreased until day 12 to half the normal value, haemoglobin remained stable and the platelet count, which was low after surgery, continued to decrease progressively until day 3. Other data are presented. Conclusion: These results, in this selected group of patients, allow a description of the “natural history” of CCRS plus HIPEC, which is not similar to classic uncomplicated postoperative courses following surgery. Knowledge of these “natural” changes may help avoid unnecessary explorations, and allow the early detection of postoperative complications. [Copyright &y& Elsevier]

Abstract: Evidence implicating Nav1.8 and TRPV1 ion channels in various chronic pain states is extensive. In this study, we used isobolographic analysis to examine the in vivo effects of the combination of the Nav1.8 blocker A-803467 [5-(4-Chloro-phenyl)-furan-2-carboxylic acid (3,5-dimethoxy-phenyl)-amide] with 2 structurally distinct TRPV1 antagonists, A-840257 [1-(1H-Indazol-4-yl)-3-([R]-4-piperidin-1-yl-indan-1-yl)-urea] or A-425619 [1-Isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea]. The antinociceptive effects of the Nav1.8 blocker alone and in combination with each TRPV1 antagonist were examined in an inflammatory (complete Freund''s adjuvant, CFA) and a neuropathic (spinal nerve ligation, SNL) pain model after systemic (intraperitoneal) administration. Alone, A-803467 was efficacious in both CFA and SNL models with ED50 values of 70 (54.2 to 95.8) mg/kg and 70 (38.1 to 111.9) mg/kg, respectively. The ED50 values of the TRPV1 antagonists A-840257 and A-425619 alone in the CFA model were 10 (3.6 to 14.9) mg/kg and 43 (24.1 to 62.2) mg/kg, respectively; both were without significant effect in the SNL model. A series of experiments incorporating 1:1, 3:1, or 0.3:1 ED50 dose-ratio combinations of A-840257 and A-803467, or A-425619 and A-803467 were performed in both pain models, and the effective doses of mixtures that produced 50% antinociception (ED50, mix) were determined by isobolographic analysis. The ED50, mix in each case was not found to be statistically different than ED50, add, the theoretical ED50 calculated assuming additive effects. These data demonstrate that Nav1.8 blockers and TRPV1 antagonists administered in combination produce an additive effect in rat pain models. Using such a combination strategy to produce analgesia may potentially provide an improved therapeutic separation from unwanted in vivo side effects associated with blockade of either Nav1.8 or TRPV1 alone. Perspective: In this report, effects of coadministration of TRPV1 antagonists and A-803467, a Nav1.8 blocker, were investigated in preclinical rodent models of neuropathic and inflammatory pain. The 2 classes of novel antinociceptive agents produced an additive interaction in attenuating CFA-induced thermal hyperalgesia, providing a rationale for their use as a combination strategy in the clinic for treating inflammatory pain. [Copyright &y& Elsevier]

Abstract: The pituitary adenylate cyclase–activating polypeptide type 1 receptor (PAC1-R) is a member of the 7-transmembrane domain, group 2 G-protein coupled receptor family. PAC1-Rs modulate neurotransmission and neurotrophic actions and have been implicated in both pronociception and antinociception. To better understand the role of PAC1-Rs in pain, PACAP 6-38, a PAC1-R antagonist, was evaluated in several inflammatory and neuropathic pain models after intrathecal (i.t.) administration. PACAP 6-38 potently reduced mechanical allodynia in a neuropathic spinal nerve ligation model (77% ± 15% maximal effect at 12 nmol, P < .01) and was also effective in reducing thermal hyperalgesia in the carrageenan model of inflammatory pain (89% ± 17% maximal effect at 12 nmol, P < .01). Although nociceptive responses were also attenuated with PACAP 6-38 in a dose-dependent manner in models of chronic inflammatory and persistent pain, no effects on motor performance were observed at analgesic doses. Taken together, these data demonstrate that blockade of the PAC1-R/PACAP complex by PACAP 6-38 can effectively attenuate thermal hyperalgesia and mechanical allodynia associated with inflammatory and neuropathic pain states. These results further emphasize that at the level of the spinal cord, PAC1-R activation is pronociceptive. Perspective: This article presents the analgesic profile generated by the blockade, at the spinal cord level, of the PAC-1 receptor by a potent peptide antagonist. This comprehensive data set demonstrates that if small molecule PAC-1 receptor antagonists could be identified, they would potentially produce broad-spectrum analgesia in both inflammatory and neuropathic pain states. [Copyright &y& Elsevier]

Abstract: A visceral pain model incorporating use of cyclophosphamide (CP) to induce bladder inflammation has been described. CP treatment in rats produces changes in behavior (abnormal postures and eye closure) and respiration rate indicative of visceral pain. We characterized the dose-dependency and progression of CP-induced cystitis pain after intraperitoneal (i.p.) CP. The behavioral and respiration rate changes were ameliorated by systemic morphine and ABT-594 [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine], a neuronal nicotinic acetylcholine receptor agonist, in a manner reversible by naloxone and mecamylamine, respectively. Sites of antinociceptive actions of morphine and ABT-594 were investigated using systemic, intrathecal (i.t.), or intracerebroventricular (i.c.v.) administration of blood-brain barrier impenetrant antagonists. Naloxone methiodide produced a complete antagonism of morphine antinociception after i.c.v. but not i.p. or i.t. administration. Chlorisondamine blocked ABT-594 antinociception after i.c.v. but not i.p. administration. Further pharmacological characterization of behavioral and respiration changes in CP-cystitis was performed using standard analgesics. The α2-adrenoceptor agonist clonidine produced a weak attenuation of CP-pain behavior. NSAIDs (ibuprofen, acetaminophen, and celecoxib) and anticonvulsants (gabapentin and lamotrigine) were without effect. These results demonstrate that morphine and ABT-594 produce antinociception in CP-cystitis by a predominantly supraspinal site of action, and that mechanisms producing robust centrally-mediated antinociception could be beneficial in cystitis pain. Perspective: In this article, potential antinociceptive effects of a variety of pharmacological agents were evaluated in a rat cystitis pain model. Morphine and a nicotinic acetylcholine receptor agonist ABT-594 were found to exert potent antinociception in this model. Findings presented here aid identification of agents to treat cystitis pain in the clinic. [Copyright &y& Elsevier]

Abstract: Residual gases having a low calorific value are by-products of many industrial combustion systems. Subsequently burning those exhaust mixture, as blast furnace gases (BFG), is a direct way to increase the overall efficiency of processes. Flame stability is a crucial issue when burning such low calorific fuels and the choice of a piloted burner with pure oxygen as oxidizer appears as an interesting option. To progress in this direction, a new concept of piloted burner is discussed in which oxycombustion of a CH4/BFG mixture is studied over a large range of global Net Calorific Value. From the results, the parameters controlling the major flame properties are determined and an attempt is made to draw a generic stability map to delineate between various combustion regimes. The burner consists of four coaxial jets. Starting from the axis of symmetry, it is composed of an oxygen (O2i) center jet, surrounded by a synthetic BFG flow, followed by a CH4 jet, and oxygen (O2e) at the periphery. The objective of such geometry is to stabilize low calorific BFG combustion with an external CH4–O2e pilot flame. The flame structure is studied according to the proportion of residual BFG gases injected. CH∗ chemiluminescence imaging is performed. Three types of flames are observed and organized in stability diagrams for such piloted non-premixed burner. In Type 1, two concentric flames are attached at the burner nozzle. In Type 2, the internal BFG flame is lifted. In Type 3, a single annulus flame burning a fuel mixture of CH4 and BFG with the external oxygen is observed. Characteristic numbers, as ratio of jets velocities and Damköhler numbers are found to control transition between the various types of flames. They are used to build the stability diagrams. [Copyright &y& Elsevier]

Studies the effects of 17alpha-dihydroequilenin sulfate, which is a component in an estrogen replacement therapy drug on atherosclerotic male and female rhesus macaques. Prevention of endothelium-dependent vasoconstriction in males and ovariectomized females; Lack of trophic effects on uterus, endometrium or breast.

Summary: There has been a resurgence of interest in the use of colistin for the treatment of multidrug-resistant Gram-negative bacterial infections. A more favorable infection outcome is observed when colistin is used in combination with carbapenems. We present a patient with severe New Delhi metallo-β-lactamase-1 Escherichia coli infection who developed convulsions rapidly followed by acute respiratory muscle weakness and apnoea during treatment with colistin and meropenem. Chromatographic assay showed a “trough” colistin level that was approximately fourfold higher than previously reported maximum steady-state colistin plasma levels in critically ill patients. The patient’s renal clearance never necessitated dose adjustments, suggesting that the observed high plasma colistin level might be due to impaired non renal elimination. Although meropenem itself has very low neurotoxic potential, its concomitant use with colistin may have elicited colistin neurotoxicity. [ABSTRACT FROM AUTHOR]

Introduction: Antibodies against Chlamydia pneumoniae are associated with the progression of abdominal aortic aneurysms (AAA), but cross-react with immunoglobulins in AAA walls indicating an autoimmune reaction. Report: Of 82 men with a small AAA followed for 1–5 years, 17% (10–27%) had antibodies against immunoglobulin, 3.7% had antinuclear antibodies (ANA), 19.5% (11–30%) had antinuclear core antibodies (ANCA), 2.4% had anti-beta-2-gpI IgG and 3,7% antibodies against cardiolipin. The presence of antibodies against immunoglobulin and ANCA were not correlated with expansion rate; 2.61 and 2.76mm/year, respectively, compared to 2.40 and 2.39mm/year annually among those without such antibodies. Discussion: Known autoantibodies are seldomly present in AAA and seem not to influence the progression of AAA. [Copyright &y& Elsevier]

L’ARN interférence, mécanisme de régulation de l’expression des gènes, est médiée par les siARNs et les microARNs, ARN non-codants de 20 à 22 nucléotides affectant la régulation post-transcriptionnelle d’ARNm cibles avec lesquels ils s’apparient. La RNase DICER est une enzyme centrale de la biosynthèse des siARNs et microARNs. Les souris dont le gène dicer est invalidé ont un phénotype complexe, et meurent très tôt pendant le développement, notamment à cause d’un défaut d’angiogenèse. Afin d’étudier l’ARN interférence au cours de l’angiogenèse embryonnaire, des souris dont le gène dicer est floxé (mutant conditionnel) sont croisées avec des souris exprimant la recombinase Cre, de manière constitutive, sous le contrôle du promoteur du gène tie2, dirigeant ainsi son expression dans les cellules endothéliales (CE) et les cellules hématopiétiques. Nos résultats montrent que l’invalidation de dicer sous le contrôle du promoteur du gène tie2 entraine une mortalité embryonnaire suite à un œdème et des hémorragies au treizième jour du développement (E13,5). L’analyse histologique montre des vaisseaux lymphatiques remplis de sang, suggérant une mauvaise séparation du réseau sanguin et lymphatique. Cette hypothèse est étudiée par marquage des vaisseaux lymphatiques (LYVE-1) et des vaisseaux sanguins (PECAM) sur embryon entier et peaux isolées à différents stades précédant la mort. Ces embryons présentent également un problème de développement du foie, probablement dû à l’activité du promoteur tie2 dans les lignées hématopoiétiques. La mise en culture de ces foies fœtaux à E13,5 révèle une atteinte des précurseurs hématopoétiques. L’étude de ces précurseurs à des stades plus précoces (E8,5) est en cours au laboratoire. Nos résultats démontrent donc un rôle important de l’ARN interférence dans le contrôle épigénétique de l’angiogenèse et de la lymphangiogenèse embryonnaire mais également dans le développement de l’hématopoièse, suggérant son implication dans la différenciation veino-lymphangiogenèse, dont les mécanismes moléculaires seront discutés. [Copyright &y& Elsevier]

Introduction: Antibodies against Chlamydia pneumoniae are associated with the progression of abdominal aortic aneurysms (AAA), but cross-react with immunoglobulins in AAA walls indicating an autoimmune reaction. Report: Of 82 men with a small AAA followed for 1–5 years, 17% (10–27%) had antibodies against immunoglobulin, 3.7% had antinuclear antibodies (ANA), 19.5% (11–30%) had antinuclear core antibodies (ANCA), 2.4% had anti-beta-2-gpI IgG and 3,7% antibodies against cardiolipin. The presence of antibodies against immunoglobulin and ANCA were not correlated with expansion rate; 2.61 and 2.76mm/year, respectively, compared to 2.40 and 2.39mm/year annually among those without such antibodies. Discussion: Known autoantibodies are seldomly present in AAA and seem not to influence the progression of AAA. [Copyright &y& Elsevier]

Abstract: Growing evidence supports a role for the immune system in the induction and maintenance of chronic pain. ATP is a key neurotransmitter in this process. Recent studies demonstrate that the glial ATP receptor, P2X7, contributes to the modulation of pathological pain. To further delineate the endogenous mechanisms that are involved in P2X7-related antinociception, we utilized a selective P2X7 receptor antagonist, A-438079, in a series of in vivo and in vitro experiments. Injection of A-438079 (10–300 μmol/kg, i.p.) was anti-allodynic in three different rat models of neuropathic pain and it attenuated formalin-induced nocifensive behaviors. Using in vivo electrophysiology, A-438079 (80 μmol/kg, i.v.) reduced noxious and innocuous evoked activity of different classes of spinal neurons (low threshold, nociceptive specific, wide dynamic range) in neuropathic rats. The effects of A-438079 on evoked firing were diminished or absent in sham rats. Spontaneous activity of all classes of spinal neurons was also significantly reduced by A-438079 in neuropathic but not sham rats. In vitro, A-438079 (1 μM) blocked agonist-induced (2,3-O-(4-benzoylbenzoyl)-ATP, 30 μM) current in non-neuronal cells taken from the vicinity of the dorsal root ganglia. Furthermore, A-438079 dose-dependently (0.3–3 μM) decreased the quantity of the cytokine, interleukin-1β, released from peripheral macrophages. Thus, ATP, acting through the P2X7 receptor, exerts a wide-ranging influence on spinal neuronal activity following a chronic injury. Antagonism of the P2X7 receptor can in turn modulate central sensitization and produce antinociception in animal models of pathological pain. These effects are likely mediated through immuno-neural interactions that affect the release of endogenous cytokines. [Copyright &y& Elsevier]

Abstract: Mortality on liver transplantation (OLT) waiting lists has increased dramatically. Until recently, non-heart-beating donors (NHBD) were not considered suitable for OLT, because of a higher risk of primary graft nonfunction (PNF) and biliary strictures. However, recent experimental/clinical evidence has indicated that NHBD-OLT is feasible when the period of warm ischemia is short. Purpose: To characterize the results of NHBD-OLT in Belgium, a survey was sent to all Belgian OLT centers. Results: Between January 2003 and November 2005, 16 livers originating from NHBD were procured and transplanted. The mean donor age was 48.8 years, including 9 males and 7 females with mean time of stop-therapy to cardiac arrest being 18 minutes and from cardiac arrest to liver cold perfusion, 10.5 minutes. Mean recipient age was 52.2 years including 12 males and 4 females. Mean cold ischemia time was 7 hours 15 minutes. No PNF requiring re-OLT was observed. Mean post-OLT peak transaminase was 2209 IU/L, which was higher among imported versus locally procured grafts. Biliary complications occurred in 6 patients requiring re-OLT (n = 2), endoscopic treatment (n = 2), surgical treatment (n = 1), or left untreated (n = 1). These tended to be more frequent after prolonged warm ischemia. Graft and patient survivals were 62.5% and 81.3%, respectively, with a follow-up of 3 to 36 months. Conclusion: This survey showed acceptable graft/patient survivals after NHBD-LT. The NHBD-liver grafts suffered a high rate of ischemic injury and biliary complications and therefore should be used carefully, namely with no additional donor risk factors, lower risk recipients, and short cold/warm ischemia. [Copyright &y& Elsevier]

Abstract: Intradermal capsaicin injection produces immediate spontaneous pain behaviors, and a secondary mechanical hypersensitivity (SMH) that is employed in the clinic as a model potentially predictive of human neuropathic pain. Presently, we have characterized capsaicin-induced SMH in rats, and compared pharmacological actions of standard analgesics in this and two nerve injury models, the L5/L6 spinal nerve ligation (SNL) and sciatic nerve chronic constriction injury (CCI) models. Intraplantar capsaicin produced dose-related SMH (enhanced paw withdrawal response to von Frey monofilament stimulation at an area away from injection site) that lasted for over 4 h. While pretreatment with a potent selective transient receptor potential vanilloid receptor-1 (TRPV1) antagonist A-425619 (1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea) prevented development of acute nocifensive (flinching) behavior immediately following capsaicin injection (ED50=4.9 mg/kg), the compound failed to attenuate the SMH when administered 2 h following capsaicin (10 μg/10 μl). Additional standard analgesics were also tested 3 h following intraplantar capsaicin in the SMH model. Comparison of their potencies in attenuating mechanical hypersensitivity in capsaicin, SNL and CCI models revealed similar ED50s for morphine (2.3 mg/kg, 1.6 mg/kg and 3.2 mg/kg, respectively), gabapentin (33.1 mg/kg, 33.9 mg/kg and 26.3 mg/kg, respectively) and lamotrigine (9.1 mg/kg, 8.9 mg/kg and 15.5 mg/kg, respectively). Duloxetine produced 50–65% effect at the highest tested dose (50 mg/kg), whereas the highest tested doses of morphine (10 mg/kg), gabapentin (85.5 mg/kg) and lamotrigine (30 mg/kg) all produced >70% efficacy in capsaicin SMH, SNL and CCI models. In contrast, celecoxib and ibuprofen showed weak effects in all three models. All standard analgesics generally had weak efficacy in attenuating capsaicin-induced immediate acute flinching behavior when administered before capsaicin. These results provide further support to the suggestions that distinct pharmacological mechanisms underlie capsaicin-induced acute nocifensive and SMH behaviors, and certain neuronal mechanisms underlying neuropathic pain states are also contributory to capsaicin-induced SMH. [Copyright &y& Elsevier]

Abstract: Short- and long-term results of liver transplantation in morbidly obese patients may be impaired compared with the general transplant population. As a consequence, severe obesity has been considered to be a relative contraindication to liver transplantation in many centers. Surgically, liver transplantation in severe obesity may be challenging. Moreover, obesity may lead to an increased rate of early and late medical complications. Herein we have reported successful liver transplantation in a super-obese patient (body mass index, 55.1 kg/m2) who had developed terminal acute-on-chronic liver disease. In the first 6 months of follow-up, the patient underwent a severe diet that led to a significant weight loss reduction to a body mass index of 39 kg/m2. This report of successful liver transplantation in a super-obese patient suggests that severe obesity should not be considered to be an absolute contraindication to liver transplantation. [Copyright &y& Elsevier]