Lysophosphatidic acid-3 receptor-mediated feed-forward production of lysophosphatidic acid: an initiator of nerve injury-induced neuropathic pain

<p>Abstract</p> <p>Background</p> <p>We previously reported that intrathecal injection of lysophosphatidylcholine (LPC) induced neuropathic pain through activation of the lysophosphatidic acid (LPA)-1 receptor, possibly via conversion to LPA by autotaxin (ATX).</p> <p>Results</p> <p>We examined <it>in vivo </it>LPA-induced LPA production using a biological titration assay with B103 cells expressing LPA₁receptors. Intrathecal administration of LPC caused time-related production of LPA in the spinal dorsal horn and dorsal roots, but not in the dorsal root ganglion, spinal nerve or sciatic nerve. LPC-induced LPA production was markedly diminished in ATX heterozygotes, and was abolished in mice that were deficient in LPA₃, but not LPA₁or LPA₂receptors. Similar time-related and LPA₃receptor-mediated production of LPA was observed following intrathecal administration of LPA. In an <it>in vitro </it>study using spinal cord slices, LPA-induced LPA production was also mediated by ATX and the LPA₃receptor. Intrathecal administration of LPA, in contrast, induced neuropathic pain, which was abolished in mice deficient in LPA₁or LPA₃receptors.</p> <p>Conclusion</p> <p>These findings suggest that feed-forward LPA production is involved in LPA-induced neuropathic pain.</p

Clinical significance of heparin-binding epidermal growth factor-like growth factor in peritoneal fluid of ovarian cancer

Epidermal growth factor receptor (EGFR) has been implicated in tumour growth and extension of ovarian cancer. Peritoneal fluid in ovarian cancer patients contains various growth factors that can promote tumour growth and extension. In order to investigate the clinical significance of EGFR ligands as activating factors of ovarian cancer, we examined the cell proliferation-promoting activity and the level of EGFR ligands in peritoneal fluid obtained from 99 patients. Proliferation-promoting activity in peritoneal fluid from 63 ovarian cancer patients (OVCA) was much higher than peritoneal fluid from 18 ovarian cyst patients (OVC) and 18 normal ovary patients (NO), and the activity was suppressed only by antibodies against EGFR or heparin-binding epidermal growth factor (HB-EGF). A large difference was observed in the level of EGFR ligands between HB-EGF and TGF-α or amphiregulin. The concentration of HB-EGF in OVCA significantly increased compared to that in OVC or NO (P<0.01). No significant difference in the concentration of TGF-α and amphiregulin was found between the OVCA and NO or OVC groups. In peritoneal fluid, HB-EGF is sufficiently elevated to activate cancer cells even at an early stage of OVCA. These results suggested that HB-EGF in peritoneal fluid might play a key role in cell survival and in the proliferation of OVCA

Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.

Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology

Moderate performance of serum S100A12, in distinguishing inflammatory bowel disease from irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>S100A12, a calcium-binding proinflammatory protein secreted by granulocytes, has been associated with different diseases of inflammatory origin, including inflammatory bowel disease (IBD). In this study, the utility of serum S100A12, in discriminating IBD from irritable bowel syndrome (IBS), was tested.</p> <p>Methods</p> <p>S100A12 serum levels were determined in 64 patients with ulcerative colitis (UC), 64 with Crohn's disease (CD) and 73 with IBS, by means of an enzyme-linked immunosorbent assay. S100A12 serum levels were evaluated with respect to the levels of known inflammatory markers and patients' characteristics.</p> <p>Results</p> <p>The median values of serum S100A12 levels were 68.2 ng/mL (range: 43.4-147.4) in UC, 70 ng/mL (41.4-169.8) in CD and 43.4 ng/mL (34.4-74.4) in IBS patients. UC and CD patients had significantly higher serum S100A12 levels compared to IBS patients (<it>P </it>= 0.001 for both comparisons). Moreover, a cut-off for serum S100A12 levels of 54.4 ng/mL could predict both UC and CD with a 66.7% sensitivity and a 64.4% specificity. The area under curve was estimated at 0.67 with a 95% confidence interval of 0.60-0.75 (<it>P </it>< 0.001). Considering standard activity indices, higher serum S100A12 levels in active compared to inactive IBD were observed, although the recorded difference did not reach statistical significance. C-reactive protein (CRP) and serum amyloid A (SAA) levels, showed a statistically significant positive correlation with S100A12 (r = 0.39, <it>P </it>= 0.001 and r = 0.23, <it>P </it>= 0.02 respectively).</p> <p>Conclusions</p> <p>Increased levels of circulating S100A12 are found in IBD, compared to IBS. When used to distinguish IBD from IBS adult patients, serum S100A12 levels exhibit moderate performance. On the other hand, serum S100A12 may serve as an inflammatory marker in IBD, since it is well correlated with CRP and SAA.</p

Social Intelligence and Academic Achievement as Predictors of Adolescent Popularity

This study compared the effects of social intelligence and cognitive intelligence, as measured by academic achievement, on adolescent popularity in two school contexts. A distinction was made between sociometric popularity, a measure of acceptance, and perceived popularity, a measure of social dominance. Participants were 512, 14–15 year-old adolescents (56% girls, 44% boys) in vocational and college preparatory schools in Northwestern Europe. Perceived popularity was significantly related to social intelligence, but not to academic achievement, in both contexts. Sociometric popularity was predicted by an interaction between academic achievement and social intelligence, further qualified by school context. Whereas college bound students gained sociometric popularity by excelling both socially and academically, vocational students benefited from doing well either socially or academically, but not in combination. The implications of these findings were discussed

Brand Suicide? Memory and Liking of Negative Brand Names

Negative brand names are surprisingly common in the marketplace (e.g., Poison perfume; Hell pizza, and Monster energy drink), yet their effects on consumer behavior are currently unknown. Three studies investigated the effects of negative brand name valence on brand name memory and liking of a branded product. Study 1 demonstrates that relative to nonnegative brand names, negative brand names and their associated logos are better recognised. Studies 2 and 3 demonstrate that negative valence of a brand name tends to have a detrimental influence on product evaluation with evaluations worsening as negative valence increases. However, evaluation is also dependent on brand name arousal, with high arousal brand names resulting in more positive evaluations, such that moderately negative brand names are equally as attractive as some non-negative brand names. Study 3 shows evidence for affective habituation, whereby the effects of negative valence reduce with repeated exposures to some classes of negative brand name

Multilingualism and the Brexit referendum

This chapter argues that the (lack of) foreign language skills has contributed to the outcome of the Brexit referendum. Theory suggests that speaking foreign languages reduces perceptions of cultural distance and contributes to the formation of transnational identities. Research also shows a link between language skills and European identity (Kuhn 2015; Díez Medrano 2018). Did Britons’ relative lack of foreign language skills play a role in the Brexit decision? Using matching methods and data from the referendum wave of the British Election Study, it is possible to estimate the effect of foreign language skills on the referendum vote. The results suggest that a significant effect of foreign language skills remains, even when taking into account education, age, gender, income, and region, party preference, and personality differences