Search

Copyright of Austral Ecology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Prey profitability is one of the most important factors influencing prey selection. This factor varies along with both prey size and handling time. Thus, large prey are generally highly profitable for consumers and boost competition. Kleptoparasitism is a form of competition in which an individual steals food previously obtained by another individual. Accordingly, handling large prey should increase the likelihood of kleptoparasitism occurrence, but these relationships remain poorly understood. Here, we studied kleptoparasitism occurrence by the Brown‐Hooded Gull (Chroicocephalus maculipennis – Laridae) on Whimbrels (Numenius phaeopus hudsonicus – Scolopacidae) preying on intertidal Mole Crabs (Emerita analoga) in a wave‐exposed sandy beach in southern Chile. Generalized linear models, fitted to data from focal‐individual video sequences, showed that kleptoparasitism probability had a positive sigmoidal response to handling time. Moreover, with an increase of 1 s in handling time, a Whimbrel doubled its probability of being kleptoparasitized. Additionally, the odds of being kleptoparasitized were 17% higher with an increase of 10 mm in prey length and 47% higher with an increase of one gull per host. However, the effect of handling on kleptoparasitism probability slightly decreased (2%) with an increase of 10 mm in prey size class. Our results suggest the existence of a threshold time in which consumers can handle their prey before kleptoparasitism probability is too high. Nevertheless, Whimbrel's mean intake rate reached 0.15 ± 0.13 kJ s−1, allowing Whimbrels to theoretically meet their energetic requirements despite losing some prey to kleptoparasites. This study provides new insight into a common form of competition among consumers, highlighting the importance of prey handling time for shorebirds with a restricted foraging time driven by tidal cycles. [ABSTRACT FROM AUTHOR]

Drought is among the main abiotic factors causing agronomical losses worldwide. To minimize its impact, several strategies have been proposed, including the use of plant growth‐promoting bacteria (PGPBs), as they have demonstrated roles in counteracting abiotic stress. This aspect has been little explored in emergent crops such as quinoa, which has the potential to contribute to reducing food insecurity. Thus, here we hypothesize that the genotype, water environment and the type of inoculant are determining factors in shaping quinoa rhizosphere bacterial communities, affecting plant performance. To address this, two different quinoa cultivars (with contrasting water stress tolerance), two water conditions (optimal and limiting water conditions) and different soil infusions were used to define the relevance of these factors. Different bacterial families that vary among genotypes and water conditions were identified. Certain families were enriched under water stress conditions, such as the Nocardioidaceae, highly present in the water‐sensitive cultivar F15, or the Pseudomonadaceae, Burkholderiaceae and Sphingomonadaceae, more abundant in the tolerant cultivar F16, which also showed larger total polyphenol content. These changes demonstrate that the genotype and environment highly contribute to shaping the root‐inhabiting bacteria in quinoa, and they suggest that this plant species is a great source of PGPBs for utilization under water‐liming conditions. [ABSTRACT FROM AUTHOR]

Intrinsic exploratory biases are an innate motivation for exploring certain types of stimuli or environments over others, and they may be associated with cognitive, emotional, and even personality‐like traits. However, their neurobiological basis has been scarcely investigated. Considering the involvement of the hippocampus in novelty recognition and in spatial and pattern separation tasks, this work researched the role of adult hippocampal neurogenesis (AHN) in intrinsic exploratory bias for a perceptually complex object in mice. Spontaneous object preference tasks revealed that both male and female C57BL/6J mice showed a consistent unconditioned preference for exploring "complex"—irregular—objects over simpler ones. Furthermore, increasing objects' complexity resulted in an augmented time of object exploration. In a different experiment, male mice received either vehicle or the DNA alkylating agent temozolomide (TMZ) for 4 weeks, a pharmacological treatment that reduced AHN as evidenced by immunohistochemistry. After assessment in a behavioral test battery, the TMZ‐treated mice did not show any alterations in general exploratory and anxiety‐like responses. However, when tested in the spontaneous object preference task, the TMZ‐treated mice did not display enhanced exploration of the complex object, as evidenced both by a reduced exploration time—specifically for the complex object—and a lack of preference for the complex object over the simple one. This study supports a novel role of AHN in intrinsic exploratory bias for perceptual complexity. Moreover, the spontaneous complex object preference task as a rodent model of "curiosity" is discussed. [ABSTRACT FROM AUTHOR]

Cocaine is a widely used psychostimulant drug whose repeated exposure induces persistent cognitive/emotional dysregulation, which could be a predictor of relapse in users. However, there is scarce evidence on effective treatments to alleviate these symptoms. Environmental enrichment (EE) has been shown to be associated with improved synaptic function and cellular plasticity changes related to adult hippocampal neurogenesis (AHN), resulting in cognitive enhancement. Therefore, EE could mitigate the negative impact of chronic administration of cocaine in mice and reduce the emotional and cognitive symptoms present during cocaine abstinence. In this study, mice were chronically administered with cocaine for 14 days, and control mice received saline. After the last cocaine or saline dose, mice were submitted to control or EE housing conditions, and they stayed undisturbed for 28 days. Subsequently, mice were evaluated with a battery of behavioural tests for exploratory activity, emotional behaviour, and cognitive performance. EE attenuated hyperlocomotion, induced anxiolytic‐like behaviour and alleviated cognitive impairment in spatial memory in the cocaine‐abstinent mice. The EE protocol notably upregulated AHN in both control and cocaine‐treated mice, though cocaine slightly reduced the number of immature neurons. Altogether, these results demonstrate that EE could enhance hippocampal neuroplasticity ameliorating the behavioural and cognitive consequences of repeated administration of cocaine. Therefore, environmental stimulation may be a useful strategy in the treatment cocaine addiction. [ABSTRACT FROM AUTHOR]

Objective: Late presenters (LP) for HIV care are associated with higher morbidity and mortality rates. Our aim was to describe the characteristics associated with LP among adolescents in Spain. Identification of particular features may help in the design of strategies for improvement. Methods: Late‐presenting adolescents diagnosed at 12–19 years of age and enrolled in the Spanish paediatric and adult HIV/AIDS cohorts (CoRIS‐CoRISpe) from 2004 to 2019 were selected. LP were defined as those presenting with CD4 count <350 cells/mm3 or an AIDS‐defining event in the 6 months following HIV diagnosis. Confirmed low CD4 count in the next 3 months and before antiretroviral treatment initiation defined confirmed LP (cLP). Results: Of 410 adolescents newly diagnosed with HIV, 303 (73.9%) had available data for assessing late presentation. Of these, 34.7% were LP and 23.7% were cLP. The median CD4 count for cLP was 235 cells/mm3 (interquartile range 122–285). In a multivariable analysis, adolescents at the highest risk of late presentation were early adolescents (age 12–14 years; odds ratio [OR] 6.50; 95% confidence interval [CI] 2.61–18.2), middle adolescents (age 15–17 years; OR 1.85; 95% CI 0.92–3.59), and adolescents born abroad (OR 1.71; 95% CI 0.97–3.00), particularly those of African origin (OR 3.08; 95% CI 1.38–6.79). Conclusions: One‐quarter of adolescents presented late for HIV care in Spain. Early adolescents, middle adolescents, and those born abroad presented a sevenfold, twofold, and twofold higher risk of being cLP, respectively. Enhancing the awareness of HIV risk and the access to care, especially for younger and foreign adolescents, could help reduce late presentation and tackle the adolescent HIV epidemic. [ABSTRACT FROM AUTHOR]

Keywords: children; COVID-19; SARS-CoV-2 EN children COVID-19 SARS-CoV-2 1974 1977 4 09/13/22 20221001 NES 221001 The massive number of infected individuals who have to be tested for SARS-CoV-2 has attracted the attention to novel diagnostic approaches, focusing on symptom-based screening.1 Some countries have emerged national testing policies, but a large number of positive children do not report any of the included symptoms in those guidelines.2 This study aimed to analyse symptoms/signs associated with SARS-CoV-2 infection among symptomatic children screened for COVID-19 and define clinical phenotypes that could differentiate COVID-19 from other infections. Manifestations and clinical phenotypes are not specific enough to predict SARS-CoV-2 infection in symptomatic children In younger children, no clinical phenotype was associated with the SARS-CoV-2 result, but in older children, the I Flu-like i phenotype was associated with positive SARS-CoV-2 (OR: 1.84 [95% CI: 1.09-3.11], I p i = 0.023) and the I Gastrointestinal i phenotype with negative SARS-CoV-2 (OR: 0.56 [95% CI: 0.34-0.91], I p i = 0.020). [Extracted from the article]

Cocaine addiction is a chronic disorder in which the person loses control over drug use. The past memories of the stimuli associated with the drug are a relevant clinical problem, since they trigger compulsive drug-seeking and drug-taking habits. Furthermore, these persistent drug-related memories seemingly coexist with cognitive decline that predicts worse therapeutic output. Here, we use a new animal model of cocaine-altered cognition that allowed to observe these events in the same individual and study their relationship. Mice were chronically administered cocaine in a conditioned place preference (CPP) apparatus for 14 days, and control mice received saline. After 28 days of cocaine withdrawal, animals were tested for retrieval of remote drug-associated memory as well as for cognitive performance in a battery of tests, including novel object and place recognition and spatial memory. The cocaine-withdrawn mice showed persistent CPP memory while impaired in the cognitive tasks, displaying deficits in reference memory acquisition and working memory. However, the CPP expression was not associated with the defective cognitive performance, indicating that they were concomitant but independent occurrences. After completion of the experiment, adult hippocampal neurogenesis (AHN) was studied as a relevant neurobiological correlate due to its potential role in both learning and drug addiction. Results suggested a preserved basal AHN in the cocaine-withdrawn mice but an aberrant learning-induced regulation of these neurons. This paradigm may be useful to investigate maladaptive cognition in drug addiction as well as related therapies. [ABSTRACT FROM AUTHOR]

Lithium battery materials can be advantageously used for the selective sequestration of lithium ions from natural resources, which contain other cations in high excess. However, for practical applications, this new approach for lithium production requires the battery host materials to be stable over many cycles while retaining the high lithium selectivity. Here, a nearly symmetrical cell design was employed to show that LiFePO4 shows good capacity retention with cycling in artificial lithium brines representative of brines from Chile, Bolivia and Argentina. A quantitative correlation was identified between brine viscosity and capacity degradation, and for the first time it was demonstrated that the dilution of viscous brines with water significantly enhanced capacity retention and rate capability. The electrochemical and X‐ray diffraction characterisation of the cycled electrodes also showed that the high lithium selectivity was preserved with cycling. Raman spectra of the cycled electrodes showed no signs of degradation of the carbon coating of LiFePO4, while scanning electron microscopy images showed signs of particle cracking, thus pointing towards interfacial reactions as the cause of capacity degradation. [ABSTRACT FROM AUTHOR]

Background: The chemokine CC motif ligand 1 (CCL1) participates in immune cell recruitment and, as other chemokines, is also involved in nociceptive processing. In contrast with previous reports indicating its participation in allodynia and cold hypernociception when spinally administered, its ability to evoke heat thermal analgesia, mediated by circulating leukocytes and endocannabinoids, after systemic administration has recently been reported. Objectives: Aiming to explore the role played by CCL1 on spinal nociception, we study here the effect of its intrathecal administration on thermal nociception in mice. Methods: Behavioral nociceptive assays, immunohistochemical experiments, white cell blood depletion procedures and qRT‐PCR experiments were performed. Results: The intrathecal administration of CCL1 (0.3–30 ng) produced analgesia as measured by the unilateral hot plate test. This effect peaked 1 h after injection, was prevented by the CCR8 antagonist R243 and was accompanied by a reduction of c‐Fos expression in spinal neurons. Whereas blood leukocyte depletion did not modify it, analgesia was abolished by the microglial inhibitor minocycline, but not the astroglial inhibitor aminoadipate. Furthermore, antinociception remained unmodified by the coadministration of cannabinoid type 1 or 2 receptors antagonists. However, it was reversed by naloxone but not by selective blockade of mu‐ or delta‐opioid receptors. The inhibitory effect induced by the selective kappa‐opioid receptor antagonist, nor‐binaltorphimine, and by an anti‐dynorphin A 1‐17 antibody indicates that analgesia evoked by spinal CCL1 is mediated by endogenous dynorphins acting on kappa‐opioid receptors. Conclusions: Endogenous dynorphin and microglia behave as key players in heat thermal analgesia evoked by spinal CCL1 in mice. [ABSTRACT FROM AUTHOR]

Improving our understanding of stability across spatial scales is crucial in the current scenario of biodiversity loss. Still, most empirical studies of stability target small scales. We experimentally removed the local space‐dominant species (macroalgae, barnacles, or mussels) at eight sites spanning more than 1000 km of coastline in north‐ and south‐central Chile, and quantified the relationship between area (the number of aggregated sites) and stability in aggregate community variables (total cover) and taxonomic composition. Resistance, recovery, and invariability increased nonlinearly with area in both functional and compositional domains. Yet, the functioning of larger areas achieved a better, albeit still incomplete, recovery than composition. Compared with controls, smaller disturbed areas tended to overcompensate in terms of total cover. These effects were related to enhanced available space for recruitment (resulting from the removal of the dominant species), and to increasing beta diversity and decaying community‐level spatial synchrony (resulting from increasing area). This study provides experimental evidence for the pivotal role of spatial scale in the ability of ecosystems to resist and recover from chronic disturbances. This knowledge can inform further ecosystem restoration and conservation policies. [ABSTRACT FROM AUTHOR]

Introduction: HIV infection causes pathological changes in the natural killer (NK) cell compartment that can be only partially restored by antiretroviral therapy (ART). We investigated NK cells phenotype and function in children with perinatally acquired HIV (PHIV) and long‐term viral control (five years) due to effective ART in a multicentre cross‐sectional European study (CARMA, EPIICAL consortium). The impact of age at ART start and viral reservoir was also evaluated. Methods: Peripheral blood mononuclear cells (PBMCs) from 40 PHIV who started ART within two years of life (early treated patients (ET), ≤6 months; late treated patients (LT), > 6 months), with at least five years of HIV‐1 suppression (<40 HIV copies/mL), were collected between November 2017 and August 2018. NK phenotype and function were analysed by flow cytometry and transcriptional profile of PBMCs by RNA‐Seq. HIV‐1 DNA was measured by real‐time polymerase chain reaction (Data were analysed by Spearman correlation plots and multivariable Poisson regression model (adjusted for baseline %CD4 and RNA HIV viral load and for age at ART start as an interaction term, either ET or LT) to explore the association between NK cell parameters and HIV reservoir modulated by age at ART start. Results: A significantly higher frequency of CD56neg NK cells was found in LT compared with ET. We further found in LT a positive correlation of CD56neg NK cells with HIV‐1 DNA. LT also displayed increased expression of the NKG2D and NKp46 activating receptors and perforin compared with ET. Moreover, CD107a+ and IFN‐γ+ frequencies in non‐stimulated NK were associated with HIV‐1 DNA in LT patients. Finally, RNA‐Seq analysis showed in LT an up‐regulation of genes related to NK‐activating pathways and susceptibility to apoptosis compared with ET. Conclusions: We show that early initiation of ART during infancy preserves the NK compartment and is associated with lower HIV‐1 reservoir. Such condition persists over adolescence due to long‐term viral control achieved through effective ART. [ABSTRACT FROM AUTHOR]

In this study, the rotating‐bending fatigue behavior in water of a 13Cr‐4Ni martensitic stainless steel as substrate, with two different thermochemical treatments and with a thermal sprayed coating was characterized. Hardness profiles were measured by instrumented nanoindentation. X‐ray diffraction was used to identify the phases and measure the residual stresses, and the fracture micromechanisms were characterized by scanning electron microscopy. The results show increases of 27%, 74%, and 95% in the fatigue strength from WC‐10Co‐4Cr coating, plasma nitriding and salt bath nitrocarburizing, respectively, compared with that untreated material at 106 cycles. The good fatigue behavior of the treated surfaces was found to result from an increase in the surface hardness and the generated compressive stresses that delay crack initiation. [ABSTRACT FROM AUTHOR]

Erasing memories of cocaine-stimuli associations might have important clinical implications for addiction therapy. Stimulating hippocampal plasticity by enhancing adult hippocampal neurogenesis (AHN) is a promising strategy because the addition of new neurons may not only facilitate new learning but also modify previous connections and weaken retrograde memories. To investigate whether increasing AHN prompted the forgetting of previous contextual cocaine associations, mice trained in a cocaine-induced conditioned place preference (CPP) paradigm were administered chronic intracerebroventricular infusions of lysophosphatidic acid (LPA, an endogenous lysophospholipid with pro-neurogenic actions), ki16425 (an LPA1/3 receptor antagonist) or a vehicle solution, and they were tested 23 days later for CPP retention and extinction. The results of immunohistochemical experiments showed that the LPA-treated mice exhibited reduced long-term CPP retention and an approximately twofold increase in the number of adult-born hippocampal cells that differentiated into mature neurons. Importantly, mediation analyses confirmed a causal role of AHN in reducing CPP maintenance. In contrast, the ki16425-treated mice displayed aberrant responses, with initially decreased CPP retention that progressively increased across the extinction sessions, leading to no effect on AHN. The pharmacological treatments did not affect locomotion or general exploratory or anxiety-like responses. In a second experiment, normal and LPA1 -receptor-deficient mice were acutely infused with LPA, which revealed that LPA1 -mediated signaling was required for LPA-induced proliferative actions. These results suggest that the LPA/LPA1 pathway acts as a potent in vivo modulator of AHN and highlight the potential usefulness of pro-AHN strategies to treat aberrant cognition in those addicted to cocaine. [ABSTRACT FROM AUTHOR]

Objective: To determine psychological distress in congenital heart disease (CHD) patients. Methods: Cross‐sectional study among consecutive CHD patients recruited from a single hospital outpatient clinic to determine anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS) questionnaire. Results: One hundred and sixty‐nine CHD patients [29 (19–39) years old, 100 (59%) males] were studied. A total of 25% and 9% of CHD patients showed anxiety and depression symptoms, respectively. Patients with an HADS score ≥ 8 had a significantly worse New York Heart Association (NYHA) functional class, needed more psychological support, had more mental health history, and took more anxiolytic/antidepressant medication than the CHD patients with an HADS score below 8. A worse NYHA functional class [OR, 1.88 (1.01–3.52)] proved to be a predictor of a borderline/abnormal HADS score. Conclusion: Psychological distress has a high prevalence among CHD patients and having an NYHA Class II and III is a significant predictor of an HADS score ≥ 8. [ABSTRACT FROM AUTHOR]

HIV co‐infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV‐infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co‐infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV–co‐infected patients and age‐ and sex‐matched vertically HCV–mono‐infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty‐seven co‐infected patients were compared with 67 matched HCV–mono‐infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co‐infected vs 20% mono‐infected had progressed to advanced fibrosis (P =.617). Peg‐IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P‐value <.001). At treatment initiation, co‐infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P <.001), and 47.1% vs 7.1% showed advanced fibrosis (P <.003), with no differences in hard‐to‐treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P =.122). In vertically HIV/HCV–co‐infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg‐IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct‐acting antivirals against HCV for vertically co‐infected patients. [ABSTRACT FROM AUTHOR]

Direct ethanol fuel cells are a promising technology for clean energy production. The ethanol oxidation reaction (EOR) is surface sensitive and, hence, the study of single‐crystal electrodes provides fundamental knowledge of the different activity of the metal crystal planes. However, for practical applications, metal nanoparticles dispersed on a porous support are generally used to enhance the efficiency and to reduce the catalyst cost. Although some research has been devoted to the development of shape‐controlled nanoparticles, the finding of an efficient, cost‐effective, and easily scaled‐up catalytic system remains a challenge. Furthermore, the use of a suitable support with a well‐defined nanoarchitecture is essential for the control of the catalyst reactivity. In this Review, a general overview of the performance of single‐crystal electrodes and unsupported/supported shape‐controlled nanoparticles for the EOR is presented, paying special attention to Pt surfaces. Finally, the major challenges and directions for future research are also discussed to guide the design of efficient shape‐controlled catalysts for the EOR. [ABSTRACT FROM AUTHOR]

A facile and straightforward methodology for the preparation of monometallic (copper and palladium) and bimetallic nanocatalysts (NiCu and PdCu) stabilized by a N‐heterocyclic carbene ligand is reported. Both colloidal and supported nanoparticles (NPs) on carbon nanotubes (CNTs) were prepared in a one‐pot synthesis with outstanding control on their size, morphology and composition. These catalysts were evaluated in the selective hydrogenation of alkynes and alkynols. PdCu/CNTs revealed an efficient catalytic system providing high selectivity in the hydrogenation of terminal and internal alkynes. Moreover, this catalyst was tested in the semi‐hydrogenation of acetylene in industrially relevant acetylene/ethylene‐rich model gas feeds and showed excellent stability even after 40 h of reaction. [ABSTRACT FROM AUTHOR]

This paper presents a detailed taphonomic study of the faunal assemblage from FLK West (Olduvai Gorge, Tanzania), a site with an Acheulean component that dates to 1.7 Ma. The faunal sample analysed here is distributed in different archaeological levels and is associated with a significant lithic accumulation including several large format tools and handaxes. The fauna indicates the proliferation of open environments similar to those found in other Bed II and late Bed I sites. Evidence of anthropogenic activity (e.g. defleshing activities and marrow consumption) has been identified in the form of cut and percussion marks. A photogrammetric and morphometric analysis suggests that these marks were produced with quartzite flakes and not with handaxes. Evidence of interaction with carnivores was also noted; tooth marks were observed on some bones. Such interaction indicates the existence of competition between humans and carnivores for the same ecological niche, and might lead us to reflect on the survival strategies of Lower Pleistocene hominins. [ABSTRACT FROM AUTHOR]

Chemokines are chemotactic cytokines whose involvement in nociceptive processing is being increasingly recognized. Based on the previous description of the involvement of CC chemokine receptor type 1 ( CCR1) in pathological pain, we have assessed the participation of CCR1 and its endogenous ligands CCL3 and CCL5 in hyperalgesia and allodynia in mice after acute inflammation with carrageenan and chronic inflammation with complete Freund's adjuvant ( CFA). The subcutaneous administration of the CCR1 antagonist J113863 (3-30 mg/kg; 30 min. before) dose dependently inhibited carrageenan- and CFA-evoked thermal hyperalgesia and mechanical allodynia produced by CFA, but not by carrageenan. The maximal dose of J113863 did not modify the increase in paw thickness induced by carrageenan or CFA. An almost ten times augmentation of CCL3 levels was detected by ELISA assays in both carrageenan and CFA paws, but not in spinal cords of inflamed mice, whereas CCL5 concentrations remained unaltered. Accordingly, a marked increase of CCL3 mRNA expression was observed in inflamed paws, with CCL3 protein detected in neutrophils and macrophages by immunohistochemical experiments. The intraplantar administration of an anti- CCL3 antibody (0.3-3 μg) blocked thermal hyperalgesia in carrageenan- and CFA-inflamed mice as well as CFA-evoked mechanical allodynia. Our data suggest that the increased concentrations of CCL3 present in inflamed tissues can be involved in acute and chronic inflammatory hyperalgesia as well as in chronic mechanical allodynia, and that these hypernociceptive symptoms can be counteracted by its neutralization with an antibody or by the blockade of CCR1 receptors. [ABSTRACT FROM AUTHOR]

Chemokine CCL2, also known as monocyte chemoattractant protein-1 ( MCP-1), is a molecule that in addition to its well-established role in chemotaxis can also act as nociceptor sensitizer. The upregulation of this chemokine in inflamed tissues could suggest its involvement in inflammatory hypernociception. Thus, we have measured CCL2 levels in mice with acute or chronic inflammation due to the intraplantar (i.pl.) injection of carrageenan or complete Freund's adjuvant ( CFA), respectively, and we have studied whether inflammatory hyperalgesia or allodynia could be attenuated by blocking CCR2 receptors or neutralizing CCL2 with an anti- CCL2 antibody. A remarkable increase in CCL2 concentration was detected by ELISA in paw homogenates coming from carrageenan- or CFA-inflamed mice, being its expression mainly localized in macrophages, as shown by immunohistochemical assays. The s.c. (0.3-3 mg/kg) or i.pl. (0.3-3 μg) administration of the CCR2 antagonist, RS 504393, dose dependently inhibited thermal hyperalgesia measured in acutely or chronically inflamed mice, whereas s.c. administration of this drug did not reduce inflammatory mechanical allodynia. Furthermore, the inhibition of inflammatory hyperalgesia after the administration of an anti- CCL2 antibody (0.1-1 μg; i.pl.) suggests that CCL2 could be the endogenous chemokine responsible for CCR2-mediated hyperalgesic effects. Besides, the acute administration of the highest antihyperalgesic dose of RS 504393 assayed did not reduce paw tumefaction or modify the presence of inflammatory cells. These results indicate that the blockade of the CCL2/ CCR2 system can counteract inflammatory hyperalgesia, being this antinociceptive effect unrelated to a decrease in the inflammatory reaction. [ABSTRACT FROM AUTHOR]

Agonists of μ-opioid receptors are currently used in the management of cancer pain. However, several data suggest that the analgesic effect of morphine can diminish during the development of experimental tumors. By using a thermal test, we have studied whether the analgesic effect evoked by morphine is altered in mice bearing two painful bone tumors. The analgesic effect evoked by systemic morphine remained unaltered after the intratibial inoculation of B16-F10 melanoma cells and was potentiated after the inoculation of NCTC 2472 osteosarcoma cells. Although the number of spinal μ-opioid receptors measured by western blot studies was not augmented in osteosarcoma-bearing mice, the analgesia evoked by intrathecal (i.t.) morphine was also enhanced. The analgesic response produced by the spinal administration of the Gi/o protein activator mastoparan was amplified, whereas the analgesic response evoked by the i.t. administration of the N-type calcium channel blocker ω-conotoxin remained unaltered. The efficacy of the GIRK channel blocker tertiapin-Q to antagonize the analgesic effect produced by a maximal dose of morphine was also increased in osteosarcoma-bearing mice. Our results seem to indicate that the analgesic effect of morphine on thermal nociception can be enhanced in response to the development of particular bone tumors in mice, being this potentiation probably related to a greater efficacy of the transduction system driven by Gi/o proteins and GIRK channels. [ABSTRACT FROM AUTHOR]