Search

Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immunohistochemistry for alpha-smooth muscle actin (a-SMA) showed an abundant periacinar distribution of α-SMAC cells in normal parathyroid glands (n = 3). This pattern was progressively lost in parathyroid adenomas (PAds; n = 6) where α-SMA+ cells were found to surround new microvessels, as observed in foetal parathyroid glands (n= 2). Moreover, in atypical adenomas (n = 5) and carcinomas (n = 4), α-SMA+ cells disappeared from the parenchyma and accumulated in the capsula and fibrous bands. At variance with normal glands, parathyroid tumours (n = 37) expressed high levels of fibroblast-activation protein (FAP) transcripts, a marker of tumour-associated fibroblasts. We analysed the ability of PAd-derived cells to activate fibroblasts using human bone-marrow mesenchymal stem cells (hBM-MSCs). PAd-derived cells induced a significant increase in FAP and vascular endothelial growth factor A (VEGFA) mRNA levels in co-cultured hBM-MSCs. Furthermore, the role of the calcium-sensing receptor (CASR) and of the CXCL12/CXCR4 pathway in the PAd-induced activation of hBM-MSCs was investigated. Treatment of co-cultures of hBM-MSCs and PAd-derived cells with the CXCR4 inhibitor AMD3100 reduced the stimulated VEGFA levels, while CASR activation by the R568 agonist was ineffective. PAd-derived cells co-expressing parathyroid hormone (PTH)/CXCR4 and PTH/CXCL12 were identified by FACS, suggesting a paracrine/autocrine signalling. Finally, CXCR4 blockade by AMD3100 reduced PTH gene expression levels in PAd-derived cells. In conclusion, i) PAd-derived cells activated cells of mesenchymal origin; ii) PAd-associated fibroblasts were involved in tumuor neoangiogenesis and iii) CXCL12/CXCR4 pathway was expressed and active in PAd cells, likely contributing to parathyroid tumour neoangiogenesis and PTH synthesis modulation. [ABSTRACT FROM AUTHOR]

Background and Purpose: It has recently been reported that oxytocin is produced by some tumour cell types, and that oxytocin receptors, belonging to the G-protein-coupled receptor (GPCR) family, are expressed in a variety of cell types. Among these, human umbilical vein endothelial cells (HUVECs) respond to oxytocin with an increased proliferation, suggesting a possible role for the hormone in the regulation of angiogenesis.Experimental Approach: We employed chemotaxis and chemoinvasion assays to characterize the effect of oxytocin on HUVEC motility, and immunoblot analysis to study its molecular mechanisms of action.Key Results: We showed that oxytocin stimulates migration and invasion in HUVECs via oxytocin receptor activation. Searching for the molecular mechanism(s) responsible for oxytocin's pro-migratory effect, we identified the Gq coupling of oxytocin receptors and phospholipase C (PLC) as the main effectors of oxytocin's action in HUVECs. We also found that oxytocin stimulates the phosphorylation of endothelial nitric oxide synthase (eNOS) via the phosphatidylinositol-3-kinase (PI-3-K)/AKT pathway, and that the activation of PI-3-K and formation of nitric oxide (NO) are required for the pro-migratory effect of oxytocin.Conclusions and Implications: The ability of oxytocin to stimulate HUVEC motility and invasion suggests that the hormone can participate in physiopathological processes where activation of endothelial cells plays an important role, for example, in angiogenesis. Interestingly, both the AKT and eNOS phosphorylation induced by oxytocin receptor activation depended on PLC activity, thus suggesting the existence of a still undefined mechanism connecting PLC to the PI-3-K/AKT pathway, upon oxytocin stimulation. [ABSTRACT FROM AUTHOR]

This article assesses hazards associated with exposure to dust in tunnels and platforms of the A and B lines of Rome's underground railway and provides an informed opinion on the risks to workers and the travelling public of exposure to tunnel dust. The study focused on the analysis and measurement of dust granulometric classes PM 10 , respirable fraction, respirable combustible dust, and the organic, metallic, siliceous, and fibrous components. Comparing the measurement values from the tunnels and platforms with those found at the entrances to the underground railway stations, it emerges that dust concentration in the tunnels and platforms is three times higher, with a maximum PM 10 value of 479 μ g/m 3 . Averaged over 24 hours, in relation to the above ground levels, drivers and station staff are exposed to an additional value of 11 μ g/m 3 and 10 μ g/m 3 , respectively. If commuters were to remain in the trains or on the station platforms, the 24-hour average exposure would increase by 3 μ g/m 3 . Iron and silica were the major components found in the dust. The use of silica sand in the emergency braking system of the carriages is capable of causing a dispersion of quartz in the air in percentages varying from 5% to 14%. Methods are suggested in this article for the reduction of dust dispersion. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare a recent multiple allergosorbent chemiluminescent assay (MAST-CLA) with the RAST for the diagnosis of inhalant allergic disease in 232 patients with rhinitis and/or bronchial asthma. As judged by concordance of clinical history, skin prick tests to a range of six allergens common to our geographic area, and by nasal provocation tests, 70 patients were non-allergic and 162 allergic: 70 to grasses, 46 to mites, four to mugwort, eight to peilitory, and 34 were sensitive to several allergens. In our patient sample that, among other things, comprises subjects with fairly rare monoallergies, MAST-CLA testing gave results which closely corresponded to positive RAST for the allergens studied, and demonstrated a close correlation with the diagnosis of inhalant-specific allergy. Our results showed that, for overall allergens, MAST-CLA was lightly less sensitive and more specific than RAST (the two in vitro tests gave an identical overall efficiency). [ABSTRACT FROM AUTHOR]

Microinjections of muscimol, a GABA receptor agonist, into the periaqueductal gray matter (PAG) counteracted the antinociceptive effect of morphine in rats, as measured by the 'tail-flick' method. Muscimol's effect was partially reversed by bicuculline. [ABSTRACT FROM AUTHOR]