Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Curcumin mediates oxaliplatin-acquired resistance reversion in colorectal cancer cell lines through modulation of CXC-Chemokine/NF-κB signalling pathway

Abstract: Resistance to oxaliplatin (OXA) is a complex process affecting the outcomes of metastatic colorectal cancer (CRC) patients treated with this drug. De-regulation of the NF-κB signalling pathway has been proposed as an important mechanism involved in this phenomenon. Here, we show that NF-κB was hyperactivated in in vitro models of OXA-acquired resistance but was attenuated by the addition of Curcumin, a non-toxic NF-κB inhibitor. The concomitant combination of Curcumin + OXA was more effective and synergistic in cell lines with acquired resistance to OXA, leading to the reversion of their resistant phenotype, through the inhibition of the NF-κB signalling cascade. Transcriptomic profiling revealed the up-regulation of three NF-κB-regulated CXC-chemokines, CXCL8, CXCL1 and CXCL2, in the resistant cells that were more efficiently down-regulated after OXA + Curcumin treatment as compared to the sensitive cells. Moreover, CXCL8 and CXCL1 gene silencing made resistant cells more sensitive to OXA through the inhibition of the Akt/NF-κB pathway. High expression of CXCL1 in FFPE samples from explant cultures of CRC patients-derived liver metastases was associated with response to OXA + Curcumin. In conclusion, we suggest that combination of OXA + Curcumin could be an effective treatment, for which CXCL1 could be used as a predictive marker, in CRC patients.

Measurement of plasma catecholamine concentrations. An assessment of anxiety.

Abstract: This study was designed to assess the value of measurement of plasma catecholamine concentrations as an objective index of anxiety. A preliminary study was undertaken on 11 healthy volunteers (medically qualified), to determine if venous cannulation per se produced any change in plasma catecholamine concentrations. There were no changes in plasma catecholamine concentrations in the 2 h following insertion of an i.v. cannula, suggesting that venous cannulation did not induce a measurable stress response. A second study was performed on 48 surgical patients who were asked to rate their perceived anxiety on a linear analogue scale immediately before premedication and immediately before induction of anaesthesia. Venous blood was obtained at the same time as these ratings. There were no significant changes in perceived anxiety or plasma noradrenaline concentrations following premedication. However, compared with values before premedication, there was a mean percentage increase in plasma adrenaline concentration of 40%before induction of anaesthesia. A significant correlation was shown between mean percentage change in Linear Analogue Anxiety Score and mean percentage change in plasma adrenaline concentrations (r = 0.32).

Randomised trial of cord clamping and initial stabilisation at very preterm birth

Abstract: Objectives For very preterm births, to compare alternative policies for umbilical cord clamping and immediate neonatal care. Design Parallel group randomised (1:1) trial, using sealed opaque numbered envelopes. Setting Eight UK tertiary maternity units. Participants 261 women expected to have a live birth before 32 weeks, and their 276 babies. Interventions Cord clamping after at least 2 min and immediate neonatal care with cord intact, or clamping within 20 s and immediate neonatal care after clamping. Main outcome measures Intraventricular haemorrhage (IVH), death before discharge. Results 132 women (137 babies) were allocated clamping ≥2 min and neonatal care cord intact, and 129 (139) clamping ≤20 s and neonatal care after clamping; six mother-infant dyads were excluded (2, 4) as birth was after 35 +6 weeks, one withdrew (death data only available) (0, 1). Median gestation was 28.9 weeks for those allocated clamping ≥2 min, and 29.2 for those allocated clamping ≤20 s. Median time to clamping was 120 and 11 s, respectively. 7 of 135 infants (5.2%) allocated clamping ≥2 min died and 15 of 135 (11.1%) allocated clamping ≤20 s; risk difference (RD) −5.9% (95% CI −12.4% to 0.6%). Of live births, 43 of 134 (32%) had IVH vs 47 of 132 (36%), respectively; RD −3.5% (−14.9% to 7.8%). There were no clear differences in other outcomes for infants or mothers. Conclusions This is promising evidence that clamping after at least 2 min and immediate neonatal care with cord intact at very preterm birth may improve outcome; a large trial is urgently needed. Trial registration ISRCTN 21456601.