Inflammation in cancer cachexia: To resolve or not to resolve (is that the question?)

Background & aims: Cachexia is associated with poor prognosis and shortened survival in cancer patients. Growing evidence points out to the importance of chronic systemic inflammation in the aetiology of this syndrome. In the recent past, chronic inflammation was considered to result from overexpression and release of pro-inflammatory factors. However, this conception is now the focus of debate, since the importance of a crescent number of pro-resolving agents in the dissolution of inflammation is now recognised - leading to the hypothesis that chronic inflammation occurs rather due to failure in the resolution process. We intend to put forward the possibility that this may also be occurring in cancer cachexia. Methods: Recent reviews on inflammation and cachexia, and on the factors involved in the resolution of inflammation are discussed. Results: The available information suggests that indeed, inflammation resolution failure may be present in cachexia and therefore we speculate on possible mechanisms. Conclusions: We emphasise the importance of studying resolution-related mechanisms in cancer cachexia and propose the opening of a new venue for cachexia treatment. (C) 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Quantum critical scaling at a Bose-glass/superfluid transition: Theory and experiment for a model quantum magnet

In this paper we investigate the quantum phase transition from magnetic Bose Glass to magnetic Bose-Einstein condensation induced by amagnetic field in NiCl2 center dot 4SC(NH2)(2) (dichloro-tetrakis-thiourea-nickel, or DTN), doped with Br (Br-DTN) or site diluted. Quantum Monte Carlo simulations for the quantum phase transition of the model Hamiltonian for Br-DTN, as well as for site-diluted DTN, are consistent with conventional scaling at the quantum critical point and with a critical exponent z verifying the prediction z = d; moreover the correlation length exponent is found to be nu = 0.75(10), and the order parameter exponent to be beta = 0.95(10). We investigate the low-temperature thermodynamics at the quantum critical field of Br-DTN both numerically and experimentally, and extract the power-law behavior of the magnetization and of the specific heat. Our results for the exponents of the power laws, as well as previous results for the scaling of the critical temperature to magnetic ordering with the applied field, are incompatible with the conventional crossover-scaling Ansatz proposed by Fisher et al. [Phys. Rev. B 40, 546 (1989)]. However they can all be reconciled within a phenomenological Ansatz in the presence of a dangerously irrelevant operator.

Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pretreatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.

Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC

We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.

Topical Treatment Using Amphotericin B and DMSO for an Atypically Located Equine Cutaneous Pythiosis

Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at flooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdomen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes. Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left flank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomori's methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue, especially located at peripheral region, where kunkers were present. Surgical excision of the mass followed by cauterization was indicated as initial treatment, and due to financial reasons, the owners elected only the topical antifungal therapy to control the fungus infection after surgery. Flunixin meglumine was also administrated for five days aiming the control of pain and inflammation. The wound was cleaned with povidone-iodine solution and rinsed with a solution containing, 50 mg, of amphotericin B in 10 mL of sterile water and 10 mL of DMSO. This procedure was carried Out twice a day. The wound healed fast due to an excellent centripetal epithelialization. and the horse was discharged after 64 days showing only 5% of the initial wound area. The owner reported by telephone the complete healing and hair growth 10 days after discharge. Discussion: Despite the atypical location of the tumoral lesion described at the present report, the history and clinical manifestations, especially the intense pruritus, showed similarity with other characteristic reports of equine cutaneous pythiosis. The diagnosis was confirmed by the histopathological examination showing hyphae structures, as described to be evidences of the presence of Pythium insidiosum in the tissue. The surgical procedure was the first step to provide remission of clinical signs, and one day after surgery the pruritus desapeared. After excision of the granulomatous tissue and cauterization, daily topical administration of amphotericin B associated with DMSO was effective in destroying the infectious agent, as observed by the excellent epithelization. A pink granulation tissue grew up providing an ideal surface for epithelial migration and the healing process progressed quickly. Centripetal epithelialization reduced the wound area until 3% of the initial area in 64 days of treatment, when the remaining wound was found almost completely healed and covered with hair. At the present report, the horse presenting pythiosis was only topically treated. The recommended therapy using amphotericin B and DMSO solution was effective, economically viable and low risk, considering that the systemic antifungal therapy usually suggested is expensive and extremely nephrotoxic. The atypical location of the lesion on the left flank shows that any anatomical region can be affected by the fungus, since the conditions for its development were present.

SUPERLINEAR ELLIPTIC PROBLEMS WITH SIGN CHANGING COEFFICIENTS

Via variational methods, we study multiplicity of solutions for the problem {-Delta u = lambda b(x)vertical bar u vertical bar(q-2)u + au + g(x, u) in Omega, u - 0 on partial derivative Omega, where a simple example for g( x, u) is |u|(p-2)u; here a, lambda are real parameters, 1 < q < 2 < p <= 2* and b(x) is a function in a suitable space L-sigma. We obtain a class of sign changing coefficients b(x) for which two non-negative solutions exist for any lambda > 0, and a total of five nontrivial solutions are obtained when lambda is small and a >= lambda(1). Note that this type of results are valid even in the critical case.

Development of osteochondrosis in Lusitano foals: A radiographic study

This study aimed to detect, by radiographic examination, the evolution of osteochondral lesions in the tarsocrural and femoropatellar joints of Lusitano foals. Within 1 month of age, 76.08% of foals had radiographic signs of osreochondrosis, but only 16.20% had lesions at 18 months. The radiographic signs resolved by 5 mo of age in most foals, but some cases that involved either joint, were not resolved until 12 mo of age. It is thought that the "age of no return" is 5 mo for the tarsocrural and 8 mo for the femoropatellar joint but this study demonstrated regression of osteochondral lesions in both joints of Lusitano foals up to 12 months of age.

Bose glass and Mott glass of quasiparticles in a doped quantum magnet

The low-temperature states of bosonic fluids exhibit fundamental quantum effects at the macroscopic scale: the best-known examples are Bose-Einstein condensation and superfluidity, which have been tested experimentally in a variety of different systems. When bosons interact, disorder can destroy condensation, leading to a 'Bose glass'. This phase has been very elusive in experiments owing to the absence of any broken symmetry and to the simultaneous absence of a finite energy gap in the spectrum. Here we report the observation of a Bose glass of field-induced magnetic quasiparticles in a doped quantum magnet (bromine-doped dichloro-tetrakis-thiourea-nickel, DTN). The physics of DTN in a magnetic field is equivalent to that of a lattice gas of bosons in the grand canonical ensemble; bromine doping introduces disorder into the hopping and interaction strength of the bosons, leading to their localization into a Bose glass down to zero field, where it becomes an incompressible Mott glass. The transition from the Bose glass (corresponding to a gapless spin liquid) to the Bose-Einstein condensate (corresponding to a magnetically ordered phase) is marked by a universal exponent that governs the scaling of the critical temperature with the applied field, in excellent agreement with theoretical predictions. Our study represents a quantitative experimental account of the universal features of disordered bosons in the grand canonical ensemble.

Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV

The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.

The growth of large mafic intrusions: Comparing Niquelandia and Ivrea igneous complexes

The Niquelandia Complex, Brazil, is one of the world's largest mafic-ultramafic plutonic complexes. Like the Mafic Complex of the Ivrea-Verbano Zone, it is affected by a pervasive high-T foliation and shows hypersolidus deformation structures, contains significant inclusions of country-rock paragneiss, and is subdivided into a Lower and an Upper Complex. In this paper, we present new SHRIMP U-Pb zircon ages that provide compelling evidence that the Upper and the Lower Niquelandia Complexes formed during the same igneous event at ca. 790 Ma. Coexistence of syn-magmatic and high-T subsolidus deformation structures indicates that both complexes grew incrementally as large crystal mush bodies which were continuously stretched while fed by pulses of fresh magma. Syn-magmatic recrystallization during this deformation resulted in textures and structures which, although appearing metamorphic, are not ascribable to post-magmatic metamorphic event(s), but are instead characteristic of the growth process in huge and deep mafic intrusions such as both the Niquelandia and Ivrea Complexes. Melting of incorporated country-rock paragneiss continued producing hybrid rocks during the last, vanishing stages of magmatic crystallization. This resulted in the formation of minor, late-stage hybrid rocks, whose presence obscures the record of the main processes of interaction between mantle magmas and crustal components, which may be active at the peak of the igneous events and lead to the generation of eruptible hybrid magmas. (C) 2012 Elsevier B.V. All rights reserved.

L-Carnitine induces recovery of liver lipid metabolism in cancer cachexia

Cancer cachexia causes metabolic alterations with a marked effect on hepatic lipid metabolism. l-Carnitine modulates lipid metabolism and its supplementation has been proposed as a therapeutic strategy in many diseases. In the present study, the effects of l-carnitine supplementation on gene expression and on liver lipid metabolism-related proteins was investigated in cachectic tumour-bearing rats. Wistar rats were assigned to receive 1 g/kg of l-carnitine or saline. After 14 days, supplemented and control animals were assigned to a control (N), control supplemented with l-carnitine (CN), tumour-bearing Walker 256 carcinosarcoma (TB) and tumour-bearing supplemented with l-carnitine (CTB) group. The mRNA expression of carnitine palmitoyltransferase I and II (CPT I and II), microsomal triglyceride transfer protein (MTP), liver fatty acid-binding protein (L-FABP), fatty acid translocase (FAT/CD36), peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and organic cation transporter 2 (OCTN2) was assessed, and the maximal activity of CPT I and II in the liver measured, along with plasma and liver triacylglycerol content. The gene expression of MTP, and CPT I catalytic activity were reduced in TB, who also showed increased liver (150%) and plasma (3.3-fold) triacylglycerol content. l-Carnitine supplementation was able to restore these parameters back to control values (p < 0.05). These data show that l-carnitine preserves hepatic lipid metabolism in tumour-bearing animals, suggesting its supplementation to be of potential interest in cachexia.

Experimental infection with Neospora caninum in pregnant bitches

In this study, transplacental transmission of Neospora caninum in bitches at different stages of pregnancy was evaluated. Three bitches were inoculated in the 3rd week and three in the 6th week of gestation with 10(8) tachyzoites of N. caninum (Nc-1 strain). All the infected bitches and at least one of their offspring presented anti-N. caninum antibodies according to the indirect fluorescent antibody test (IFAT > 400). The pups and their mothers were sacrificed and tissues from the central nervous system (CNS), popliteal lymph nodes, skeletal muscle, brain, lungs, heart and liver were analyzed for the presence of N. caninum using the nested polymerase chain reaction (nested PCR), restriction fragment length polymorphism (RFLP) and immunohistochemistry (IHC). The parasite was found in the pups in lymph node, CNS, heart and liver tissues using nested PCR. There was no difference in perinatal mortality between the offspring from bitches infected in the 3rd week of gestation (60%) and in the 6th week (53.8%).