Ehrlich tumor induces TRPV1-dependent evoked and non-evoked pain-like behavior in mice

We standardized a model by injecting Ehrlich tumor cells into the paw to evaluate cancer pain mechanisms and pharmacological treatments. Opioid treatment, but not cyclooxygenase inhibitor or tricyclic antidepressant treatments reduces Ehrlich tumor pain. To best use this model for drug screening it is essential to understand its pathophysiological mechanisms. Herein, we investigated the contribution of the transient receptor potential cation channel subfamily V member 1 (TRPV1) in the Ehrlich tumor-induced pain model. Dorsal root ganglia (DRG) neurons from the Ehrlich tumor mice presented higher activity (calcium levels using fluo-4 fluorescent probe) and an increased response to capsaicin (TRPV1 agonist) than the saline-injected animals

Education can improve the negative perception of a threatened long-lived scavenging bird, the Andean condor

Human-wildlife conflicts currently represent one of the main conservation problems for wildlife species around the world. Vultures have serious conservation concerns, many of which are related to people's adverse perception about them due to the belief that they prey on livestock. Our aim was to assess local perception and the factors influencing people's perception of the largest scavenging bird in South America, the Andean condor. For this, we interviewed 112 people from Valle Fértil, San Juan province, a rural area of central west Argentina. Overall, people in the area mostly have an elementary education, and their most important activity is livestock rearing. The results showed that, in general, most people perceive the Andean condor as an injurious species and, in fact, some people recognize that they still kill condors. We identified two major factors that affect this perception, the education level of villagers and their relationship with livestock ranching. Our study suggests that conservation of condors and other similar scavengers depends on education programs designed to change the negative perception people have about them. Such programs should be particularly focused on ranchers since they are the ones who have the worst perception of these scavengers. We suggest that highlighting the central ecological role of scavengers and recovering their cultural value would be fundamental to reverse their persecution and their negative perception by people.Fil: Cailly Arnulphi, Verónica Beatríz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Lambertucci, Sergio Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Borghi, Carlos Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; Argentin

Longitudinal evaluation the pulmonary function of the pre and postoperative periods in the coronary artery bypass graft surgery of patients treated with a physiotherapy protocol

<p>Abstract</p> <p>Background</p> <p>The treatment of coronary artery disease (CAD) seeks to reduce or prevent its complications and decrease morbidity and mortality. For certain subgroups of patients, coronary artery bypass graft surgery (CABG) may accomplish these goals. The objective of this study was to assess the pulmonary function in the CABG postoperative period of patients treated with a physiotherapy protocol.</p> <p>Methods</p> <p>Forty-two volunteers with an average age of 63 ± 2 years were included and separated into three groups: healthy volunteers (n = 09), patients with CAD (n = 9) and patients who underwent CABG (n = 20). Patients from the CABG group received preoperative and postoperative evaluations on days 3, 6, 15 and 30. Patients from the CAD group had evaluations on days 1 and 30 of the study, and the healthy volunteers were evaluated on day 1. Pulmonary function was evaluated by measuring forced vital capacity (FVC), maximum expiratory pressure (MEP) and Maximum inspiratory pressure (MIP).</p> <p>Results</p> <p>After CABG, there was a significant decrease in pulmonary function (p < 0.05), which was the worst on postoperative day 3 and returned to the preoperative baseline on postoperative day 30.</p> <p>Conclusion</p> <p>Pulmonary function decreased after CABG. Pulmonary function was the worst on postoperative day 3 and began to improve on postoperative day 15. Pulmonary function returned to the preoperative baseline on postoperative day 30.</p

Therapeutic activity of lipoxin A4 in TiO2-induced arthritis in mice: NF-κB and Nrf2 in synovial fluid leukocytes and neuronal TRPV1 mechanisms

BackgroundLipoxin A4 (LXA4) has anti-inflammatory and pro-resolutive roles in inflammation. We evaluated the effects and mechanisms of action of LXA4 in titanium dioxide (TiO2) arthritis, a model of prosthesis-induced joint inflammation and pain.MethodsMice were stimulated with TiO2 (3mg) in the knee joint followed by LXA4 (0.1, 1, or 10ng/animal) or vehicle (ethanol 3.2% in saline) administration. Pain-like behavior, inflammation, and dosages were performed to assess the effects of LXA4in vivo.ResultsLXA4 reduced mechanical and thermal hyperalgesia, histopathological damage, edema, and recruitment of leukocytes without liver, kidney, or stomach toxicity. LXA4 reduced leukocyte migration and modulated cytokine production. These effects were explained by reduced nuclear factor kappa B (NFκB) activation in recruited macrophages. LXA4 improved antioxidant parameters [reduced glutathione (GSH) and 2,2-azino-bis 3-ethylbenzothiazoline-6-sulfonate (ABTS) levels, nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and Nrf2 protein expression], reducing reactive oxygen species (ROS) fluorescent detection induced by TiO2 in synovial fluid leukocytes. We observed an increase of lipoxin receptor (ALX/FPR2) in transient receptor potential cation channel subfamily V member 1 (TRPV1)+ DRG nociceptive neurons upon TiO2 inflammation. LXA4 reduced TiO2‐induced TRPV1 mRNA expression and protein detection, as well TRPV1 co-staining with p-NFκB, indicating reduction of neuronal activation. LXA4 down-modulated neuronal activation and response to capsaicin (a TRPV1 agonist) and AITC [a transient receptor potential ankyrin 1 (TRPA1) agonist] of DRG neurons.ConclusionLXA4 might target recruited leukocytes and primary afferent nociceptive neurons to exert analgesic and anti-inflammatory activities in a model resembling what is observed in patients with prosthesis inflammation

Budlein A, a Sesquiterpene Lactone From Viguiera robusta, Alleviates Pain and Inflammation in a Model of Acute Gout Arthritis in Mice

Background: Gout is the most common inflammatory arthritis worldwide. It is a painful inflammatory disease induced by the deposition of monosodium urate (MSU) crystals in the joints and peri-articular tissues. Sesquiterpene lactones (SLs) are secondary metabolite biosynthesized mainly by species from the family Asteraceae. It has been demonstrated that SLs present anti-inflammatory, analgesic, antitumoral, antiparasitic, and antimicrobial activities. In this study, we aimed at evaluating the efficacy of the SL budlein A in a model of acute gout arthritis in mice.Methods: Experiments were conducted in male Swiss or male LysM-eGFP mice. Animals were treated with budlein A (1 or 10 mg/kg) or vehicle 30 min before stimulus with MSU (100 μg/10 μL, intra-articular). Knee joint withdrawal threshold and edema were evaluated using electronic von Frey and caliper, respectively, 1–15 h after MSU injection. Leukocyte recruitment was determined by counting cells (Neubauer chamber), H&amp;E staining, and using LysM-eGFP mice by confocal microscopy. Inflammasome components, Il-1β, and Tnf-α mRNA expression were determined by RT-qPCR. IL-1β and TNF-α production (in vitro) and NF-κB activation (in vitro and in vivo) were evaluated by ELISA. In vitro analysis using LPS-primed bone marrow-derived macrophages (BMDMs) was performed 5 h after stimulation with MSU crystals. For these experiments, BMDMs were either treated or pre-treated with budlein A at concentrations of 1, 3, or 10 μg/mL.Results: We demonstrated that budlein A reduced mechanical hypersensitivity and knee joint edema. Moreover, it reduced neutrophil recruitment, phagocytosis of MSU crystals by neutrophils, and Il-1β and Tnf-α mRNA expression in the knee joint. In vitro, budlein A decreased TNF-α production, which might be related to the inhibition of NF-κB activation. Furthermore, budlein A also reduced the IL-1β maturation, possibly by targeting inflammasome assembly in macrophages.Conclusion: Budlein A reduced pain and inflammation in a model of acute gout arthritis in mice. Therefore, it is likely that molecules with the ability of targeting NF-κB activation and inflammasome assembly, such as budlein A, are interesting approaches to treat gout flares

Trans-Chalcone Attenuates Pain and Inflammation in Experimental Acute Gout Arthritis in Mice

Gouty arthritis is characterized by an intense inflammatory response to monosodium urate crystals (MSU), which induces severe pain and reduction in the life quality of patients. Trans-Chalcone (1,3-diphenyl-2-propen-1-one) is a flavonoid precursor presenting biological activities such as anti-inflammatory and antioxidant proprieties. Thus, the aim of this work was to evaluate the protective effects of trans-Chalcone in experimental gout arthritis in mice. Mice were treated with trans-Chalcone (3, 10, or 30 mg/kg, per oral) or vehicle (Tween 80 20% plus saline) 30 min before intra-articular injection of MSU (100 μg/knee joint, intra-articular). We observed that trans-Chalcone inhibited MSU-induced mechanical hyperalgesia, edema, and leukocyte recruitment (total leukocytes, neutrophils, and mononuclear cells) in a dose-dependent manner. Trans-Chalcone also decreased inflammatory cell recruitment as observed in Hematoxylin and Eosin (HE) staining and the intensity of fluorescence of LysM-eGFP+ cells in the confocal microscopy. Trans-Chalcone reduced MSU-induced oxidative stress as observed by an increase in the antioxidant defense [Glutathione (GSH), Ferric Reducing (FRAP), and 2,2’-Azinobis-3-ethylbenzothiazoline 6-sulfonic acid (ABTS assays)] and reduction in reactive oxygen and nitrogen species production [superoxide anion (NBT assay) and nitrite (NO assay)]. Furthermore, it reduced in vivo MSU-induced interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α), and IL-6 production, and increased Transforming growth factor-β (TGF-β) production. Importantly, trans-Chalcone reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and thereby the mRNA expression of the inflammasome components Nlrp3 (cryopyrin), Asc (apoptosis-associated speck-like protein containing a CARD), Pro-caspase-1 and Pro-IL-1β. In vitro, trans-Chalcone reduced the MSU-induced release of IL-1β in lipopolysaccharide (LPS)-primed macrophages. Therefore, the pharmacological effects of trans-Chalcone indicate its therapeutic potential as an analgesic and anti-inflammatory flavonoid for the treatment of gout

[Ru(bpy)2(NO)SO3](PF6), a Nitric Oxide Donating Ruthenium Complex, Reduces Gout Arthritis in Mice

Monosodium urate crystals (MSU) deposition induces articular inflammation known as gout. This disease is characterized by intense articular inflammation and pain by mechanisms involving the activation of the transcription factor NFκB and inflammasome resulting in the production of cytokines and oxidative stress. Despite evidence that MSU induces iNOS expression, there is no evidence on the effect of nitric oxide (NO) donors in gout. Thus, the present study evaluated the effect of the ruthenium complex donor of NO {[Ru(bpy)2(NO)SO3](PF6)} (complex I) in gout arthritis. Complex I inhibited in a dose-dependent manner MSU-induced hypersensitivity to mechanical stimulation, edema and leukocyte recruitment. These effects were corroborated by a decrease of histological inflammation score and recruitment of Lysm-eGFP+ cells. Mechanistically, complex I inhibited MSU-induced mechanical hypersensitivity and joint edema by triggering the cGMP/PKG/ATP-sensitive K (+) channels signaling pathway. Complex I inhibited MSU-induced oxidative stress and pro-inflammatory cytokine production in the knee joint. These data were supported by the observation that complex I inhibited MSU-induced NFκB activation, and IL-1β expression and production. Complex I also inhibited MSU-induced activation of pro-IL-1β processing. Concluding, the present data, to our knowledge, is the first evidence that a NO donating ruthenium complex inhibits MSU-induced articular inflammation and pain. Further, complex I targets the main physiopathological mechanisms of gout arthritis. Therefore, it is envisaged that complex I and other NO donors have therapeutic potential that deserves further investigation

The AGILE Mission

AGILE is an Italian Space Agency mission dedicated to observing the gamma-ray Universe. The AGILE's very innovative instrumentation for the first time combines a gamma-ray imager (sensitive in the energy range 30 MeV-50 GeV), a hard X-ray imager (sensitive in the range 18-60 keV), a calorimeter (sensitive in the range 350 keV-100 MeV), and an anticoincidence system. AGILE was successfully launched on 2007 April 23 from the Indian base of Sriharikota and was inserted in an equatorial orbit with very low particle background. Aims. AGILE provides crucial data for the study of active galactic nuclei, gamma-ray bursts, pulsars, unidentified gamma-ray sources, galactic compact objects, supernova remnants, TeV sources, and fundamental physics by microsecond timing. Methods. An optimal sky angular positioning (reaching 0.1 degrees in gamma- rays and 1-2 arcmin in hard X-rays) and very large fields of view (2.5 sr and 1 sr, respectively) are obtained by the use of Silicon detectors integrated in a very compact instrument. Results. AGILE surveyed the gamma- ray sky and detected many Galactic and extragalactic sources during the first months of observations. Particular emphasis is given to multifrequency observation programs of extragalactic and galactic objects. Conclusions. AGILE is a successful high-energy gamma-ray mission that reached its nominal scientific performance. The AGILE Cycle-1 pointing program started on 2007 December 1, and is open to the international community through a Guest Observer Program