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The role of eosinophilia in atopic diseases, including asthma, is well established, as is the well-known role of IL-5 as a major eosinophilopoeitin and chemoattractant. Following influenza A virus infection of mice, type 2 innate lymphoid cells are recruited to the respiratory tract and produce large quantities of IL-5, which contributes to the recruitment of eosinophils into the infected lungs during the recovery phase of infection. We demonstrate here that while IL-5 is required for optimal recovery from influenza A virus infection in BALB/c and C57BL/6 mice, the protective effect of IL-5 is independent of eosinophils, suggesting an alternative cellular target. We describe the unexpected finding of IL-5 receptor alpha (CD125) expression on neutrophils infiltrating the inflamed mouse lungs, as well as on neutrophils at other anatomic sites. We extend this finding of neutrophil CD125 expression to humans, specifically to neutrophils found in the bronchoalveolar lavage fluid from the inflamed lungs of children with treatment-refractory asthma. We further demonstrate that the IL-5 receptor on neutrophils is capable of signal transduction. Our data provide further evidence that neutrophils can play a role bridging atopic type 2 and innate anti-microbial immunity.

Background and purpose: We recently demonstrated the existence of strain differences in self‐administration of the cannabinoid CB1 receptor agonist WIN55,212‐2 (WIN) by Long Evans (LE) and Lister Hooded (LH) but not Sprague‐Dawley (SD) male rats. This follow‐up study is aimed at verifying whether sex and ovarian hormones might also be critical factors in the initiation, retention and extinction of WIN self‐administration. Experimental approach: LE, LH and SD male and female rats, the latter either intact or bilaterally ovariectomized (OVX), were trained to self‐administer WIN (12.5 μg kg−1 per infusion) under a FR1 reinforcement schedule, using lever‐pressing. Key results: Data showed that contrary to the findings in SD rats, LE and LH rats developed robust cannabinoid intake, with rates of responding for WIN being constantly higher in intact females than in males (+45 and +42% for LE and LH strains, respectively). In comparison with intact females, OVX females of both strains acquired self‐administration at lower rates, displaying slower acquisition, lower drug intake (−42 and −52% for LE and LH, respectively) and longer extinction. Conclusions and implications: These findings provide the first evidence of significant sex differences in cannabinoid self‐administration, females acquiring stable WIN intake at higher rates and more rapidly than males. Moreover, when compared to intact females, a lower percentage of LE and LH OVX rats acquired and maintained stable drug intake, suggesting that ovarian hormones might represent a critical factor in modulating the reinforcing effect of cannabinoids. British Journal of Pharmacology (2007) 152, 795–804; doi:10.1038/sj.bjp.0707465; published online 24 September 2007

Aim: Sperm chromatin/DNA integrity is essential for the accurate transmission of paternal genetic information, and normal sperm chromatin structure is important for sperm fertilizing ability. The routine examination of semen, which includes sperm concentration, motility and morphology, does not identify defects in sperm chromatin structure. The origin of sperm DNA damage and a variety of methods for its assessment are described. Evaluation of sperm DNA damage appears to be a useful tool for assessing male fertility potential both in vivo and in vitro. The possible impact of sperm DNA defects on the offspring is also discussed.

In this study we analyzed the ESR signal of alanine dosimeters with gadolinium exposed to 6 MV linear accelerator photons. We observed that the addition of gadolinium brings about an improvement in the sensitivity to photons because of its high atomic number. The experimental data indicated that the addition of gadolinium increases the sensitivity of the alanine to 6 MV photons. This enhancement was better observed at high gadolinium concentrations for which the tissue equivalence is heavily reduced. However, information about the irradiation setup and of the radiation beam features allows one to correct for this difference. Monte Carlo simulations were carried out to obtain information on the expected effect of the addition of gadolinium on the dose absorbed by the alanine molecules inside the pellets. These results are compared with the experimental values, and the agreement is discussed.

Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether Δ-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long–Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28–49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 μg/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 μg/kg/infusion) and greater responding for moderate–low heroin doses (dose–response curve: 7.5, 15, 30, 60, and 100 μg/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, μ opioid receptor ( μ OR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. μ OR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

We recently provided evidence for a functional link between cannabinoid and opioid endogenous systems in relapse to heroin‐seeking behaviour in rats. In the present study, we aimed at investigating whether the previously observed cross‐talk between cannabinoids and opioids could be extended to mechanisms underlying relapse to cannabinoid‐seeking behaviour after a prolonged period of abstinence. In rats previously trained to intravenously self‐administer the synthetic cannabinoid receptor (CB1) agonist WIN 55,212‐2 (12.5 μg kg−1 inf−1) under a fixed ratio (FR1) schedule of reinforcement, noncontingent nonreinforced intraperitoneal (i.p.) priming injections of the previously self‐administered CB1 agonist (0.25 and 0.5 mg kg−1) as well as heroin (0.5 mg kg−1), but not cocaine (10 mg kg−1), effectively reinstate cannabinoid‐seeking behaviour following 3 weeks of extinction. The selective CB1 receptor antagonist SR 141716A (0.3 mg kg−1 i.p.) does not reinstate responding when given alone, but completely prevents the cannabinoid‐seeking behaviour triggered by WIN 55,212‐2 or heroin primings. The nonselective opioid antagonist naloxone (1 mg kg−1 i.p.) has no effect on operant behaviour per sè, but significantly blocks cannabinoid‐ and heroin‐induced reinstatement of cannabinoid‐seeking behaviour. These results provide the first evidence of drug‐induced reinstatement of cannabinoid‐seeking behaviour, and further strengthen previous findings on a cross‐talk between the endogenous cannabinoid and opioid systems in relapse mechanisms to drug‐seeking. British Journal of Pharmacology (2004) 143, 343–350. doi:10.1038/sj.bjp.0705932

Sudden cardiac death is the leading cause of death in the industrialized world, with the majority of such tragedies being due to ventricular fibrillation 1 . Ventricular fibrillation is a frenzied and irregular disturbance of the heart rhythm that quickly renders the heart incapable of sustaining life. Rotors, electrophysiological structures that emit rotating spiral waves, occur in several systems that all share with the heart the functional properties of excitability and refractoriness. These re-entrant waves, seen in numerical solutions of simplified models of cardiac tissue 2 , may occur during ventricular tachycardias 3 , 4 . It has been difficult to detect such forms of re-entry in fibrillating mammalian ventricles 5 , 6 , 7 , 8 . Here we show that, in isolated perfused dog hearts, high spatial and temporal resolution mapping of optical transmembrane potentials can easily detect transiently erupting rotors during the early phase of ventricular fibrillation. This activity is characterized by a relatively high spatiotemporal cross-correlation. During this early fibrillatory interval, frequent wavefront collisions and wavebreak generation 9 are also dominant features. Interestingly, this spatiotemporal pattern undergoes an evolution to a less highly spatially correlated mechanism that lacks the epicardial manifestations of rotors despite continued myocardial perfusion.

Objectives: To obtain knowledge on male reproductive toxicity of inorganic lead at current European exposure levels and to establish lowest adverse effect levels, if any. Methods: A cross sectional survey of the semen of 503 men employed by 10 companies was conducted in the United Kingdom, Italy, and Belgium. The mean blood lead concentration was 31.0 μg/dl (range 4.6–64.5) in 362 workers exposed to lead and 4.4 μg/dl (range below the detection limit of 19.8) in 141 reference workers. Semen volume and sperm concentration were determined in a fresh semen sample according to an agreed protocol subject to quality assurance. The sperm chromatin structure assay (SCSA) was performed at a centralised laboratory. Extraneous determinants including centre, period of sexual abstinence, and age were taken into account in the statistical analysis. If appropriate, possible thresholds were examined by iterative threshold slope linear regression. Results: The median sperm concentration was reduced by 49% in men with blood lead concentration above 50 μg/dl. There was no indication of a linear trend of lower sperm concentration with increasing blood lead values, but threshold slope least square regression identified a blood lead concentration of 44 μg/dl (β=−0.037, F=4.35, p=0.038) as a likely threshold. Abnormal sperm chromatin structure was not related to blood lead concentration, but some indications of deterioration of sperm chromatin was found in men with the highest concentrations of lead within spermatozoa. Biological monitoring data did not indicate long term effects of lead on semen quantity or sperm chromatin. Conclusion: Adverse effects of lead on sperm concentration and susceptibility to acid induced denaturation of sperm chromatin are unlikely at blood lead concentrations below 45 μg/dl. Effects of low level exposure to lead on other measures of testicular function cannot be ruled out.

This study examines the hydrogeological hazard associated with the construction of the proposed Skalička Dam in the vicinity of the Hranice Karst. Prompted by the catastrophic regional floods in 1997 and 2010, the design of the dam aims to mitigate floods along the Bečva River downstream of the reservoir. However, concerns have been raised regarding the potential disturbance of the natural groundwater regime in the Hranice Karst and the source of mineral waters for the Teplice spa. This is due in particular to the dam's location in an area with limestone outcrops potentially susceptible to surface-water infiltration. Previous studies have also highlighted the strong correlation between the water level in the Bečva River and the water level in karst formations such as the Hranice Abyss, Zbrašov Aragonite Caves, and other caves in the locality. To address these concerns, a nonlinear reservoir-pipe groundwater flow model was employed to simulate the behaviour of the Hranice Karst aquifer and specifically the effects of the dam reservoir's impoundment. The study concluded that the lateral variant of the dam would have a practically negligible impact on the karst water system, with the rise in water level being only a few centimetres. The through-flow variant was found to have a more significant potential impact on water levels and the outflow of mineral water to the spa, with a piezometric rise of about 1 m and an increase in the karst water discharge to the Bečva River of more than 50 %. Based on these results, recommendations for further investigations concerning the design of the dam and its eventual construction have been formulated to reduce geological uncertainties and to minimize the potential impact of the hydraulic scheme on the hydrogeology of the karstic system.