Characterization of Antiallodynic Actions of ALE-0540, a Novel Nerve Growth Factor Receptor Antagonist, in the Rat1

There is growing evidence that nerve growth factor (NGF) may function as a mediator of persistent pain states. We have identified a novel nonpeptidic molecule, ALE-0540, that inhibits the binding of NGF to tyrosine kinase (Trk) A or both p75 and TrkA (IC50 5.88 6 1.87 mM, 3.72 6 1.3 mM, respectively), as well as signal transduction and biological responses mediated by TrkA receptors. ALE-0540 was tested in models of neuropathic pain and thermally-induced inflammatory pain, using two routes of administration, a systemic i.p. and a spinal intrathecal (i.th.) route. Morphine was also tested for comparison in the antiallodynia model using mechanical stimuli. We show that either i.p. or i.th. administration of ALE-0540 in rats produced antiallodynia in the L5/L6 ligation model of neuropathic pain. The calculated A50 values (and 95% confidence intervals) for ALE- 0540 administered i.p. and i.th. were 38 (17.5– 83) mg/kg and 34.6 (17.3– 69.4) mg, respectively. ALE-0540 given i.th., at doses of 30 and 60 mg, also blocked tactile allodynia in the thermal sensitization model. Although morphine displayed greater potency [A50 value of 7.1 (5.6–8.8) mg/kg] than ALE- 0540 in anti-allodynic effect when given i.p. to L5/L6-ligated rats, it was not active when administered i.th. These data suggest that a blockade of NGF bioactivity using a NGF receptor antagonist is capable of blocking neuropathic and inflammatory pain and further support the hypothesis that NGF is involved in signaling pathways associated with these pain states. ALE-0540 represents a nonpeptidic small molecule which can be used to examine mechanisms leading to the development of agents for the treatment of pain

Prospective Study of Pre-Gravid Sugar-Sweetened Beverage Consumption and the Risk of Gestational Diabetes Mellitus

ObjectiveConsumption of sugar-sweetened beverages (SSBs) was related to an elevated risk of type 2 diabetes and insulin resistance in several recent studies among middle- or older-aged populations. Studies on SSB consumption and glucose intolerance among pregnant women, however, are lacking. We therefore examined the association between regular SSB consumption before pregnancy and the risk of gestational diabetes mellitus (GDM).Research design and methodsThis was a prospective study among 13,475 U.S. women who reported at least one singleton pregnancy between 1992 and 2001 in the Nurses' Health Study II. GDM was self-reported and validated by medical record review in a subsample. Cox proportional hazards models with multivariate adjustments were applied to examine the association of SSB consumption with GDM risk.ResultsDuring 10 years of follow-up, 860 incident GDM case subjects were identified. After adjustment for age, parity, race, physical activity, smoking, alcohol intake, prepregnancy BMI, and Western dietary pattern, intake of sugar-sweetened cola was positively associated with the risk of GDM, whereas no significant association was found for other SSBs and diet beverages. Compared with women who consumed <1 serving/month, those who consumed >or=5 servings/week of sugar-sweetened cola had a 22% greater GDM risk (relative risk 1.22 [95% CI 1.01-1.47]).ConclusionsFindings from this study suggest that prepregnancy higher consumption of sugar-sweetened cola (>or=5 servings/week) is associated with an elevated GDM risk, whereas no significant association with GDM risk was observed for other SSBs and diet beverages

Micromechanical modeling of tension stiffening in FRP-strengthened concrete elements

This article presents a micromodeling computational framework for simulating the tensile response and tension-stiffening behavior of fiber reinforced polymer–strengthened reinforced concrete elements. The total response of strengthened elements is computed based on the local stress transfer mechanisms at the crack plane including concrete bridging stress, reinforcing bars stress, FRP stress, and the bond stresses at the bars-to-concrete and fiber reinforced polymer-to-concrete interfaces. The developed model provides the possibility of calculating the average response of fiber reinforced polymer, reinforcing bars, and concrete as well as the crack spacing and crack widths. The model, after validation with experimental results, is used for a systematic parameter study and development of micromechanics-based relations for calculating the crack spacing, fiber reinforced polymer critical ratio, debonding strength, and effective bond length. Constitutive models are also proposed for concrete tension stiffening and average response of steel reinforcing bars in fiber reinforced polymer–strengthened members as the main inputs of smeared crack modeling approaches

Stress-corrosion mechanisms in silicate glasses

The present review is intended to revisit the advances and debates in the comprehension of the mechanisms of subcritical crack propagation in silicate glasses almost a century after its initial developments. Glass has inspired the initial insights of Griffith into the origin of brittleness and the ensuing development of modern fracture mechanics. Yet, through the decades the real nature of the fundamental mechanisms of crack propagation in glass has escaped a clear comprehension which could gather general agreement on subtle problems such as the role of plasticity, the role of the glass composition, the environmental condition at the crack tip and its relation to the complex mechanisms of corrosion and leaching. The different processes are analysed here with a special focus on their relevant space and time scales in order to question their domain of action and their contribution in both the kinetic laws and the energetic aspects.Comment: Invited review article - 34 pages Accepted for publication in J. Phys. D: Appl. Phy

Development of a composite prototype with GFRP profiles and sandwich panels used as a floor module of an emergency house

A series of experimental tests carried out on a composite prototype to be used as a floor module of an emergency house is presented in this paper. The prototype comprises a frame structure formed by GFRP pultruded profiles, and two sandwich panels constituted by GFRP skins and a polyurethane foam core that configures the floor slab. The present work is part of the project “ClickHouse – Development of a prefabricated emergency house prototype made of composites materials” and investigates the feasibility of the assemblage process of the prototype and performance to support load conditions typical of residential houses. Furthermore, sandwich panels are also independently tested, analysing their flexural response, failure mechanisms and creep behaviour. Obtained results confirm the good performance of the prototype to be used as floor module of an emergency housing, with a good mechanical behaviour and the capacity of being transported to the disaster areas in the form of various low weight segments, and rapidly installed. Additionally, finite element simulations were carried out to assess the stress distributions in the prototype components and to evaluate the global behaviour and load transfer mechanism of the connections.Quadro de Referência Estratégica Nacional (QREN)FEDER funds through the Operational Program for Competitiveness Factors – COMPETE and the Portuguese National Agency of Innovation (ADI) - project no. 3896

New Mediterranean Biodiversity Records (April 2015)

The Collective Article ‘New Mediterranean Biodiversity Records’ of the Mediterranean Marine Science journal offers the means to publish biodiversity records in the Mediterranean Sea. The current article is divided in two parts, for records of native and alien species respectively. The new records of native fish species include: the slender sunfish Ranzania laevis and the scalloped ribbonfish Zu cristatus in Calabria; the Azores rockling Gaidropsarus granti in Calabria and Sicily; the agujon needlefish Tylosu¬rus acus imperialis in the Northern Aegean; and the amphibious behaviour of Gouania willdenowi in Southern Turkey. As regards molluscs, the interesting findings include Ischnochiton usticensis in Calabria and Thordisa filix in the bay of Piran (Slovenia). The stomatopod Parasquilla ferussaci was collected from Lesvos island (Greece); the isopod Anilocra frontalis was observed parasit¬izing the alien Pteragogus trispilus in the Rhodes area. The asteroid Tethyaster subinermis and the butterfly ray Gymnura altavela were reported from several localities in the Greek Ionian and Aegean Seas.The new records of alien species include: the antenna codlet Bregmaceros atlanticus in Saronikos Gulf; three new fish records and two decapods from Egypt; the establishment of the two spot cardinal fish Cheilodipterus novemstriatus and the first record of the marble shrimp Saron marmoratus in semi-dark caves along the Lebanese coastline; the finding of Lagocephalus sceleratus, Sargocentron rubrum, Fistularia commersonii and Stephanolepis diaspros around Lipsi island (Aegean Sea, Greece); the decapod Penaeus Hathor in Aegean waters; the decapod Penaeus aztecus and the nudibranch Melibe viridis in the Dodecanese islands; the finding of Pinctada imbricata radiate in the Mar Grande of Taranto (Ionian Sea, Italy) and the Maliakos Gulf (Greece)

New Mediterranean Biodiversity Records (December 2017)

The “New Mediterranean Biodiversity Records” series includes new records of marine species found in the Mediterranean basin and/or information on the spatial distribution of already established species of particular interest. The current article presents information on 20 marine taxa classified per country according to their geographic position in the Mediterranean, from west to east. The new records per ecoregion are as follows: Algeria: the first record of the fish Etrumeus golanii is reported along the Algerian coast. Tunisia: the alien jellyfish Phyllorhiza punctata is reported for the first time in the Gulf of Gabès. Italy: the first record of Siganus rivulatus in the Strait of Sicily and a new record of Katsuwonus pelamis from the central Tyrrhenian Sea are reported. The establishment of the isopod of the genus Mesanthura in the northern Tyrrhenian with some notes on its ecology are also included. Croatia: signs of establishment of the Lessepsian Siganus luridus and the occurrence of the alien mollusc Rapana venosa are reported. Albania: the first record of the elasmobranch Alopias superciliosus and a recent sighting of the rare monk seal Monachus monachus in Albanian waters are given. Greece: signs of the establishment of the fish Parupeneus forsskali and of the ascidian Hermania momus in Hellenic Aegean waters are reported. Turkey: a new record of the fish P. forsskali and of the Acarea of the genus Acaromantis and Simognathus are given, while the first case of Remora australis in association with delphinids and the occurrence of the sea star Coscinasterias tenuispina are reported. Also, the establishment of the two alien species Isognomon legumen and Viriola sp. [cf. corrugata] are presented. Egypt: the fish Bathygobius cyclopterus is reported for the first time in Mediterranean Sea waters. Also, a new record of Pagellus bogaraveo and a first record of Seriola fasciata in Egyptian Mediterranean waters are reported. Lebanon: the first record of Dondice banyulensis is presented

Clinical Significance of Cartilage Biomarkers for Monitoring Structural Joint Damage in Rheumatoid Arthritis Patients Treated with Anti-TNF Therapy

PURPOSE: With the current use of biologics in rheumatoid arthritis (RA), there is a need to monitor ongoing structural joint damage due to the dissociation of articular cartilage damage from disease activity of RA. This study longitudinally analyzed levels of serum cartilage biomarkers during 54 weeks of infliximab therapy, to evaluate the feasibility of biomarkers for monitoring structural joint damage. METHODS: Subjects comprised 33 patients with early RA and 33 patients with established RA. All patients received 3 mg/kg of infliximab and methotrexate for 54 weeks. Levels of the following serum cartilage markers were measured at baseline and at weeks 14, 22, and 54: hyaluronan (HA); cartilage oligometric matrix protein (COMP); type II collagen (CII)-related neoepitope (C2C); type II procollagen carboxy-propeptide (CPII); and keratin sulfate (KS). Time courses for each biomarker were assessed, and relationships between these biomarkers and clinical or radiographic parameters generally used for RA were investigated. RESULTS: Levels of CRP, MMP-3, DAS28-CRP, and annual progression of TSS were improved to similar degrees in both groups at week 54. HA and C2C/CPII were significantly decreased compared to baseline in the early RA group (p<0.001), whereas HA and COMP, but not C2C/CPII, were decreased in the established RA group. Strikingly, serum C2C/CPII levels were universally improved in early RA, regardless of EULAR response grade. Both ΔHA and ΔC2C/CPII from baseline to week 54 correlated significantly with not only ΔCRP, but also ΔDAS28 in early RA. Interestingly, when partial correlation coefficients were calculated by standardizing CRP levels, the significant correlation of ΔHA to ΔDAS28 disappeared, whereas correlations of ΔC2C/CPII to ΔDAS28, ΔJNS, and ΔHAQ remained significant. These results suggest a role of ΔC2C/CPII as a marker of ongoing structural joint damage with the least association with CRP, and that irreversible cartilage damage in established RA limits restoration of the C2C/CPII level, even with tight control of joint inflammation. CONCLUSION: The temporal course of C2C/CPII level during anti-TNF therapy indicates that CII turnover shifts toward CII synthesis in early RA, but not in established RA, potentially due to irreversible cartilage damage. ΔC2C/CPII appears to offer a useful marker reflecting ongoing structural joint damage, dissociated from inflammatory indices such as CRP and MMP-3