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: Vasopeptidase inhibitors are drugs that inhibit angiotensin-converting enzyme and neutral endopeptidase (NEP). The latter is a protease that degrades vasoactive peptides and is increased in diabetes. We have previously shown that treating streptozotocin-induced diabetic rats, an animal model of type 1 diabetes, with AVE7688, a vasopeptidase inhibitor, improves neurovascular and neural function. In this study, we determined the effect of treating Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes, with AVE7688 on vascular and neural function.', 'ZDF rats at 12 weeks of age were treated for 12 weeks with AVE7688 (500 mg/kg diet). Afterwards, vascular reactivity of epineurial arterioles of the sciatic nerve and nerve conduction velocity and blood flow was determined.', 'Vascular and neural function was significantly impaired in ZDF rats compared with age-matched lean (control) rats. Treating ZDF rats with AVE7688 improved vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Motor and sensory nerve conduction velocity, endoneurial blood flow and thermal nociception end-points were also improved by treatment compared with untreated ZDF rats. Superoxide and expression of NEP were increased in epineurial arterioles from ZDF rats and attenuated by treatment with AVE7688.\Question: Does treatment of Zucker diabetic fatty rats with AVE7688 improve vascular and neural dysfunction?

SOLUTION: AVE7688 is an effective treatment for microvascular and neural disease in ZDF rats. Thus, vasopeptidase inhibitors may be an effective treatment for diabetic microvascular and neural complication in type 2 diabetes.

PROBLEM: Context: Esophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing 2 entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen-driven, TH2-associated allergic disorder, whereas the cause of PPI-REE remains a mystery.', 'In this study, our aim was to investigate the pathogenesis of PPI-REE by using a recently described EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts and to determine whether PPI therapy reverses any esophageal transcriptional abnormalities.', 'We evaluated the EDP signature in biopsy samples obtained from adult and pediatric patients with PPI-REE from 4 institutions and compared the pre- and post-PPI therapy expression profiles of these subjects with those of patients with active EoE.', 'The EDP differentiated patients with EoE from control subjects with 100% accuracy among the 4 clinical sites. Bioinformatics analysis revealed largely overlapping transcriptomes between patients with PPI-REE and those with EoE, including the genes for eosinophil chemotaxis (eotaxin 3, CCL26), barrier molecules (desmoglein 1, DSG1), tissue remodeling (periostin, POSTN), and mast cells (carboxypeptidase A, CPA3). PPI monotherapy alone almost completely reversed the allergic inflammatory transcriptome of patients with PPI-REE. Furthermore, we identified a set of candidate genes to differentiate patients with EoE from those with PPI-REE before treatment.\Question: Does transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveal proton pump inhibitor-reversible allergic inflammation?

SOLUTION: These findings provide definitive evidence that PPI-REE is a disease entity with significant molecular overlap with EoE, suggesting that many patients with PPI-REE represent a continuum of the same pathogenic allergic mechanisms that underlie EoE and thus might constitute a subphenotype of patients with EoE. The ability of PPI therapy to nearly entirely reverse gene expression associated with PPI-REE, particularly that associated with classic features of allergic inflammation, provides new insight into potential disease etiology and management strategies for patients with significant esophageal eosinophilia.

PROBLEM: Context: To investigate whether the level of plasminogen activator (PA) activity assayed in gastrointestinal carcinomas and the "morphologically normal tissues" adjacent to them is associated with the degree of tumor progression.', 'Tumor and "normal tissues" were obtained from gastrointestinal surgical samples to assess urokinase-type (u-PA) and tissue-type plasminogen activator (t-PA) activities by radial caseinolytic assay and the expression of PA inhibitor-1 (PAI-1) by ELISA. We compared the PA system between the tumor and "normal tissues" and we investigated the existence of correlations between: (a) PA production in the tumor and "normal tissues", (b) different components of the PA system, and (c) PA system and the degree of tumor progression.', '(1) Total PA activity, u-PA activity and PAI-1 expression are significantly higher in tumor than in "normal tissues", whereas t-PA activity does not differ between them. (2) Total PA activity mainly correlates with u-PA activity in tumor tissues and similarly with u-PA and t-PA activities in "normal tissues". (3) There is a significant association between t-PA activity in tumor and "normal tissues" and the degree of tumor progression.\Question: Is tissue-type plasminogen activator activity in morphologically normal tissues adjacent to gastrointestinal carcinomas associated with the degree of tumor progression?

SOLUTION:
"Morphologically normal tissues" adjacent to carcinomas present abnormal t-PA activity that is associated with the degree of tumor progression. Assaying of this activity could be useful as a predictive parameter.