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: Bradykinin is a neuropeptide released after tissue damage which plays an important role in inflammatory pain. The up-regulation of the bradykinin B1 receptor in response to inflammation makes it an attractive target for drug development. Aim was to investigate if the selective B1 receptor antagonist BI113823 reduces inflammation-induced mechanical hyperalgesia and if the effect is mediated via peripheral and/or spinal B1 receptor antagonism.', "Electrophysiological recordings of peripheral afferents and spinal neurons were combined with behavioural experiments to better understand the underlying mechanisms of B1 receptor antagonism. Experiments were performed 24h after injection of complete Freund's adjuvant (CFA) or saline into the paw of Wistar rats. A gene expression analysis for the B1 receptor was performed in different tissues. BI113823 was administered orally or intrathecally to assess effects on CFA-induced hyperalgesia. Peripheral afferents of the saphenous nerve as well as spinal wide dynamic range (WDR) and nociceptive-specific (NS) neurons were recorded, and mechanosensitivity was measured before and after BI113823 administration.", 'BI113823 reduced CFA-induced mechanical hyperalgesia when administered orally or intrathecally. An increased B1 receptor gene expression was found in peripheral and spinal neural tissue. BI113823 significantly reduced mechanosensitivity of peripheral afferents and spinal NS neurons, but had no effect on WDR neurons.
Answer: The selective bradykinin B1 receptor antagonist BI113823 reduces CFA-induced mechanical hyperalgesia which is mediated via antagonism of peripheral as well as spinal bradykinin B1 receptors. The selective modulation of CFA-sensitized spinal NS neurons by BI113823 could be a promising property for the treatment of inflammatory pain.

SOLUTION: Does the bradykinin B1 receptor antagonist BI113823 reverse inflammatory hyperalgesia by desensitization of peripheral and spinal neurons?

PROBLEM: Context: Adipose tissue is responsible for releasing various adipokines that have been related to insulin resistance. Understanding the relationship of these adipokines to insulin resistance may foster the development of new treatments for diabetes.', 'The primary objective of this study was to determine whether an association between retinol-binding protein 4 (RBP4) and insulin resistance exists in nonobese individuals without a family history or diagnosis of diabetes. The secondary objective was to determine by a dual energy x-ray absorptiometry scan which adipose tissue depot most closely relates to RBP4 levels.', 'Cross-sectional analysis of 92 study participants ranging in age from 20 to 83 yr was performed. The range of body mass index (BMI) was from 18 to 30 kg/m(2). Exclusion criteria were a BMI greater than 30 kg/m(2), family history of diabetes, or a diagnosis of diabetes. Insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp. Body fat was measured by dual energy x-ray absorptiometry scan.', 'RBP4 values were lower in females (35.8 +/- 1.7 microg/ml) compared with males (39.9 +/- 1.4 microg/ml; P = 0.06). RBP4 levels were found to correlate negatively with insulin sensitivity (r = -0.32; P = 0.002) and positively with age (r = 0.38; P < 0.001). RBP4 levels did not correlate with BMI (r = -0.13; P = 0.22), trunk fat (r = 0.16; P = 0.22), or percent body fat (r = 0.07; P = 0.65). However, RBP4 levels did correlate with percent trunk fat (r = 0.36; P = 0.001).
Answer: These findings indicate a relationship between RBP4, insulin sensitivity, and percent trunk fat in individuals who may not have features of insulin resistance.

SOLUTION: Is retinol-binding protein 4 associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes?

PROBLEM: Context: Factors influencing alloimmunization to transfused red blood cells (RBCs) are not well understood. Utilizing a murine model, we have recently reported that RBC alloimmunization is enhanced by recipient treatment with viral-like polyinosinic polycytidylic acid (poly(I:C)). To determine whether a different subtype of inflammation also enhances RBC alloimmunization, we investigated the effects of the bacterial endotoxin lipopolysaccharide (LPS) on alloimmunization.', 'Mice were treated with poly(I:C) or LPS; in select experiments, the precursor frequency of naive antigen-specific CD4+ T cells was increased using T cells from T-cell receptor transgenic mice. Recipients were transfused with leukoreduced RBCs expressing the membrane-bound hen egg lysozyme (mHEL) antigen, and alloimmunization was measured by anti-HEL immunoglobulin G responses using enzyme-linked immunosorbent assay and flow cytometric cross-match. Costimulatory molecule expression was examined on antigen-presenting cells (APCs) by flow cytometry.', 'Increased expression of costimulatory molecules on APCs was seen after treatment with either poly(I:C) and LPS. In contrast to the enhancement of RBC alloimmunization observed after treatment with poly(I:C), LPS not only failed to enhance but also actively suppressed alloimmunization, even in the presence of increased mHEL-specific CD4+ T cells (p < 0.001 LPS vs. control).
Answer: These data demonstrate that the regulation of RBC alloimmunization by inflammatory stimuli is complex, including enhancement by a viral-like stimulus and suppression by a bacterial-type stimulus. The mechanism(s) are unlikely to involve variation in the costimulatory molecules studied, because only subtle differences on APCs were observed after treatment with poly(I:C) and LPS.

SOLUTION:
Do discrete Toll-like receptor agonists have differential effects on alloimmunization to transfused red blood cells?