TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Intrathecal adenosine is antinociceptive under conditions of central sensitization, but not in response to acute stimuli in normals. The reasons for this selective circumstance of action remain unclear, but some evidence links adenosine's antinociceptive effects to release of norepinephrine by terminals in the spinal cord. The purpose of this study was to test whether spinal adenosine induces norepinephrine release selectively in settings of hypersensitivity.", 'Rats randomly assigned to spinal nerve ligation, sham operation, or no operation were anesthetized. A microdialysis fiber was implanted in the spinal cord dorsal horn at the L5-L6 level and perfused with artificial cerebrospinal fluid. After washout and a baseline sample period, adenosine at various concentrations was infused through the fiber for 150 min, and samples were collected every 15 min.', "In ligated, but not in sham or normal animals, adenosine perfusion increased norepinephrine in spinal cord microdialysates in a concentration-dependent manner. The effects of adenosine plateaued after 75 min and remained stable until the end of the experiment. Intravenous injection of selective adenosine A1 and A2 receptor antagonists revealed that adenosine's effect on spinal norepinephrine release was A1 receptor mediated.\Question: Does intraspinal adenosine induce spinal cord norepinephrine release in spinal nerve-ligated rats but not in normal or sham controls?

SOLUTION: This is the first study to provide direct evidence that adenosine is able to release norepinephrine in spinal cord dorsal horns in living animals. However, this effect was only seen in animals after spinal nerve ligation. These data are consistent with behavioral studies demonstrating that adenosine's antinociceptive effects in rats after spinal nerve ligation is totally dependent on intact spinal noradrenergic terminals and can be blocked by spinal alpha 2-adrenergic receptor antagonists.

PROBLEM: Context: Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established.', 'Prostate cancer cases (N = 191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N = 209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used to estimate associations.', 'Of note, 86.2% of cases and 78.2% of controls had at least one biopsy core (of three assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 [95% confidence interval (CI), 1.04-3.06] times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7-10, N = 94; OR, 2.24; 95% CI, 1.06-4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their prostate-specific antigen (PSA) was low (<2 ng/mL at biopsy).\Question: Is chronic inflammation in benign prostate tissue associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial?

SOLUTION: Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high grade. The association did not seem to be due to detection bias.

PROBLEM: Context: The pathogenesis of aortic dilatation in patients with congenital aortic valve anomalies is poorly understood. Recent studies suggest that alterations of gene expression may be related to ascending aortic aneurysm formation in these patients. Knockout of endothelial nitric oxide synthase (eNOS) and GATA5 is associated with bicuspid aortic valves in mice. To study the role of eNOS and GATA5 in human congenital aortic valve disease and aortic dilatation, we investigated their gene expression in aortic tissue from patients with unicuspid, bicuspid, and tricuspid aortic valves.', 'Samples from 84 patients (33 tricuspid, 32bicuspid, and 19 unicuspid) were harvested intraoperatively from the ascending aorta. GATA5 and eNOS expression was determined by real-time polymerase chain reaction.', 'GATA5 and eNOS expression in the aortic wall from patients with unicuspid aortic valves (GATA5: mean [M], 2.14; standard deviation [SD], 1.72; eNOS: M, 3.40; SD, 3.83) was significantly higher than in tricuspid aortic valves (GATA5: M, 1.12; SD, 0.80; eNOS: M, 1.00; SD, 0.74; each p < 0.05). Patients with bicuspid aortic valves (GATA5: M, 1.29, SD, 1.33; eNOS: M, 1.66; SD, 1.31) had a significantly higher eNOS expression than patients with tricuspid aortic valves (p < 0.05). The expression levels of eNOS and GATA5 correlated positively with each other and negatively with the ascending aortic diameter.\Question: Is gATA5 and endothelial nitric oxide synthase expression in the ascending aorta related to aortic size and valve morphology?

SOLUTION:
Our data suggest that GATA5, possibly through upregulation of eNOS, plays a role in the development of aortic dilatation in patients with unicuspid and bicuspid aortic valves. The differential gene expression in patients with unicuspid compared with bicuspid aortic valves suggests that the pathogenesis of both aortic valve anomalies may be different.