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1.  EUK-207 protects human intestinal microvascular endothelial cells (HIMEC) against irradiation-induced apoptosis through the Bcl2 pathway 
Life sciences  2012;91(15-16):771-782.
Aim
To elucidate the signaling mechanisms involved in the protective effect of EUK-207 against irradiation-induced cellular damage and apoptosis in human intestinal microvasculature endothelial cells (HIMEC).
Methods
HIMECs were irradiated and treated with EUK-207. Using hydroethidine and DCF-DA fluorescent probe the intracellular superoxide and reactive oxygen species (ROS) were determined. By real-time PCR and western blotting caspase-3, Bcl2 and Bax genes and proteins were analyzed. Proliferation was determined by [3H]-thymidine uptake. Immunofluorescence staining was used for translocation of p65 NFκB subunit.
Key finding
Irradiation increased ROS production, apoptosis, Bax, Caspase3 and NFkB activity in HIMEC and inhibited cell survival/growth/proliferation. EUK-207 restored the endothelial functions, markedly inhibited the ROS, up-regulated the Bcl2 and down-regulated Bax and prevented NFκB caspase 3 activity in HIMEC.
Significance
HIMEC provide a novel model to define the effect of irradiation induced endothelial dysfunction. Our findings suggest that EUK-207 effectively inhibits the damaging effect of irradiation.
doi:10.1016/j.lfs.2012.08.018
PMCID: PMC3520131  PMID: 22940617
HIMEC; Irradiation; superoxide dismutase; oxyradical; EUK-207; NFκB
2.  Neuronal Plasticity in the Cingulate Cortex of Rats following Esophageal Acid Exposure in Early Life 
Gastroenterology  2011;141(2):544-552.
Background & Aims
The cingulate cortex (CC) has been reported to be involved in processing pain of esophageal origin. However, little is known about molecular changes and cortical activation that arise from early-life, esophageal acid reflux. Excitatory neurotransmission via activation of the N-methyl-D-aspartate (NMDA) receptor and its interaction with post-synaptic density protein-95 (PSD-95) at the synapse appears to mediate neuronal development and plasticity. We investigated the effect of early-life esophageal acid exposure on NMDA receptor subunits and PSD-95 expression in the developing CC.
Methods
We assessed NMDA receptor subunits and PSD-95 protein expression in rostral CC (rCC) tissues of rats exposed to esophageal acid or saline (control), either during post-natal days 7–14 (P7–P14) and/or acutely, at adult stage (P60), using immunoblot and immunoprecipitation analyses.
Results
Compared with controls, acid exposure from P7 to P14 significantly increased expression of NR1, NR2A, and PSD-95, measured 6 weeks after exposure. However, acute exposure at P60 caused a transient increase in expression of NMDA receptor subunits. These molecular changes were more robust in animals exposed to acid neonatally and rechallenged, acutely, at P60. Esophageal acid exposure induced calcium calmodulin kinase II-mediated phosphorylation of the subunit NR2B at Ser1303.
Conclusions
Esophageal acid exposure during early stages of life has long-term effects, because of phosphorylation of the NMDA receptor and overexpression in the rCC. This molecular alteration in the rCC might mediate sensitization of patients with acid-induced esophageal disorders.
doi:10.1053/j.gastro.2011.04.044
PMCID: PMC3152593  PMID: 21616075
brain; developmental neuroscience; pain processing; CamKII
3.  Neonatal Cystitis-Induced Colonic Hypersensitivity in Adult Rats: A Model of Viscero-Visceral Convergence 
Background
The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms.
Methods
Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days (postnatal days 14th–16th). The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissue. CRD or urinary bladder distension (UBD)-sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N-methyl-D-aspartic acid (NMDA) NR1 subunit in the L6-S1 spinal cord was examined using Western blot.
Results
The VMR to CRD (≥10mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD-sensitive PNAs from the zymosan rats was significantly higher than the control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (p > 0.05). The expression of spinal NR1 subunit was significantly higher in zymosan-treated rats compared to saline treated rats (p <0.05).
Conclusion
Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD-sensitive PNAs. Neonatal cystitis does results in overexpression of spinal NR1 subunit in adult rats.
doi:10.1111/j.1365-2982.2011.01724.x
PMCID: PMC3117950  PMID: 21592255
cystitis; visceral hyperalgesia; neonatal; viscero-visceral convergence

Results 1-3 (3)