TASK DEFINITION: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Context: The mechanism involved in AD is complex, which has prompted to develop compounds that could simultaneously interact with several potential targets. Here, we report a new synthesized compound SCR-1693 which is designed to target both AChE and calcium channels that are potential for AD therapy.', 'We investigated the effects of SCR-1693 on AChE and calcium channels, the effects of neuroprotection and anti-amnesia in icv-Aβ25-35-injected mice, and the potential mechanisms.', 'AChE activity assay, intracellular Ca(2+) content and calcium currents measurement, and Aβ25-35-induced cellular death determine were performed for validation of designed targets and neuroprotection of SCR-1693. Mice were orally administrated with SCR-1693 once daily after an Aβ25-35 injection. The Morris water maze and Y-maze test, and hippocampal protein detection were conducted on days 5-10, day 11, and day 8. The pyramidal neuron number, hippocampal AChE activity, and synaptic transmission were measured on day 12.', 'SCR-1693 acted as a selective, reversible, and noncompetitive inhibitor of AChE, and a nonselective voltage-gated calcium channel blocker. SCR-1693 also inhibited the increase of AChE activity in the mouse hippocampus. SCR-1693 was more effective than donepezil and memantine in preventing Aβ25-35-induced long-term and short-term memory impairment, maintaining the basal transmission of Schaffer collateral-CA1 synapses, and sustaining LTP in mouse hippocampus. SCR-1693 attenuated Aβ25-35-induced death of SH-SY5Y cell and the loss of hippocampal pyramidal neurons, and regulated Aβ25-35-induced signal cascade in neurons.
Answer: All these findings indicated that SCR-1693, as a double-target-direction agent, is a considerable candidate for AD therapy.

SOLUTION: Does a novel acetylcholinesterase inhibitor and calcium channel blocker SCR-1693 improve Aβ25-35-impaired mouse cognitive function?

PROBLEM: Context: The etiology and pathogenesis of inflammatory bowel disease remain unknown. However, neutrophil infiltration into the inflammatory lesion is an important process in inflammatory bowel disease. In this study, we used rat trinitrobenzene sulfonic acid (TNBS) ileitis as a Crohn's disease model, and investigated the effects of oral IS-741 (which inhibits the expression of Mac-1, a cell adhesion molecule) on leukocyte-endothelial interactions.", 'Rat ileitis was induced by the intraluminal injection of a TNBS solution (160 mg/kg in 50% ethanol) at a site 10 cm proximal to the ileocecal valve. The rats then received oral IS-741 (50 mg/kg) or saline for 7 days. On the day 8 after the initial administration of IS-741 or saline, we determined the visible damage score, and assessed myeloperoxidase (MPO) activity. Concentrations of cytokines in the ileum, such as interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were assayed by enzyme-linked immunosorbent assay (ELISA). We also investigated the infiltration of polymorphonuclear cells and Mac-1 positive cells by histological examinations.', 'The administration of IS-741 resulted in a significant reduction of the visible damage score, myeloperoxidase (MPO) activity, and mucosal IL-8 levels in the ileum as compared with the saline administration. IS-741 also dramatically reduced the infiltration of polymorphonuclear cells and Mac-1 positive cells into the inflamed lesions.
Answer: These results indicate that the oral administration of IS-741 inhibits neutrophil infiltration into inflamed lesions, and is effective for attenuating rat TNBS ileitis. This new anti-inflammatory agent may be beneficial for the treatment of inflammatory bowel disease.

SOLUTION: Does a novel diamino-pyridine derivative ( IS-741 ) attenuate rat ileitis induced by trinitrobenzene sulfonic acid?

PROBLEM: Context: Acute kidney injury (AKI) is common after liver transplantation (OLT) and is associated with high morbidity and mortality. Previous studies have shown that interleukin-18 (IL-18) levels are associated with AKI. The purpose of this study was to determine whether plasma IL-18 levels were early predictors for AKI after liver transplantation.', 'Plasma samples were obtained from 26 patients who underwent OLT at induction of anesthesia (T1), 1 hour after the surgical incision (T2), the time of reperfusion (T3), as well as 1 (T4), 2 (T5), and 4 hours (T6) after reperfusion. Samples were also obtained at 24 hours after surgery (T7). The AKI criteria were taken according to the Acute Kidney Injury Network criteria.', 'Twelve patients (46%) developed AKI after OLT. The area under the receiver operating curve of plasma IL-18 concentrations (T4/T1) to predict AKI occurrence was 0.842 at T5, 0.905 at T6, 0.726 at T7, and 0.726 at T5 to T7.
Answer: Plasma IL-18 concentrations taken 1 hour after reperfusion were predictive of AKI. Therefore, changing IL-18 ratio may be an early predictor for AKI after OLT.

SOLUTION:
Is the ratio of plasma interleukin-18 a sensitive biomarker for acute kidney injury after liver transplantation?