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: To investigate the effects of interval aerobic training combined with strength-endurance exercise (IASE) and caloric restriction (CR) on body composition, glycaemic and lipid profile and inflammatory markers.', 'Thirty-two Zucker diabetic fatty rats were randomised into 4 groups (sedentary\xa0+\xa0CR; sedentary\xa0+\xa0adlibitum; IASE\xa0+\xa0CR; and IASE\xa0+\xa0adlibitum). Training groups conducted an IASE programme in the same session, 5 days/week for 2 months. Body weight, fat and muscle mass and body water were measured using a body composition analyser. Plasma total, LDL and HDL cholesterol, phospholipids, triglycerides, insulin, adiponectin, tumour necrosis factor alpha, interleukin 1 and 10 were measured. Blood fasting and postprandial glucose were assessed. Body weight was lower in the CR compared to the adlibitum groups (p\xa0<\xa00.001). Fat mass was lower in the CR compared to the adlibitum (p\xa0<\xa00.05) and in the IASE compared to the sedentary groups (p\xa0<\xa00.001), but IASE increased lean mass (p\xa0<\xa00.001). Triglycerides were lower in the CR compared to the adlibitum groups (p\xa0<\xa00.001) whereas total and LDL-cholesterol and fasting glucose were reduced only in the IASE groups (all, p\xa0<\xa00.001). Phospholipids decreased in the CR compared to the adlibitum (p\xa0<\xa00.05) and the IASE compared to the sedentary groups (p\xa0<\xa00.001). The area under the curve after oral glucose tolerance test, insulin and homoeostatic model assessment were lower in the IASE and the CR compared to the sedentary and adlibitum groups, respectively (all, p\xa0<\xa00.001). Adiponectin was lower in the CR groups (p\xa0<\xa00.001).\Question: Does interval aerobic training combined with strength-endurance exercise improve metabolic markers beyond caloric restriction in Zucker rats?

SOLUTION: Overall, IASE as well as CR were both useful interventions, especially when combined. However, IASE showed greater improvements on body composition, inflammatory and glycaemic profile than CR did.

PROBLEM: Context: To demonstrate the effect in vivo of the myocilin gene mutation Thr377Met on outflow facility of aqueous humor, as measured by tonography.', 'Forty-two members of a pedigree known to carry the Thr377Met mutation were examined for glaucoma, evaluated with tonography, and screened for myocilin mutations. Tonography was used to calculate the coefficient of aqueous outflow facility (C), as well as the ratio of the resting intraocular pressure to C (P(0)/C). Subjects were reexamined for glaucoma 5 years after tonography.', "Seven subjects were excluded because of previous treatment known to alter facility of aqueous outflow. The mean outflow facility of the eyes of the 12 subjects carrying the Thr377Met mutation was significantly reduced compared with the 23 non-carriers' eyes using both C (P<0.001) and P(0)/C (P<0.001). Reduced outflow facility was also demonstrated in those mutation carriers who were not yet expressing clinical signs of glaucoma or ocular hypertension when measured using C (P = 0.015) and P(0)/C (P = 0.001). After 5 years, progression towards glaucoma had occurred in 5 of the myocilin mutation-carriers, 2 of whom showed bilateral progression; 3 carriers remained completely normal. Four subjects had bilateral glaucoma at the outset and remained unchanged. The carriers' eyes that progressed towards glaucoma had reduced outflow facility compared with those that remained normal, although the difference was not statistically significant.\Question: Does tonography demonstrate reduced facility of outflow of aqueous humor in myocilin mutation carriers?

SOLUTION: Carriers of the myocilin Thr377Met mutation have reduced outflow facility, which may be detected prior to developing glaucoma. Tonography was not seen to be clinically useful in predicting progression towards glaucoma.

PROBLEM: Context: Thrombin is generated in significant quantities during cardiopulmonary bypass and mediates adverse events, such as platelet aggregation and proinflammatory responses, through activation of the high-affinity thrombin receptor protease-activated receptor 1, which is expressed on platelets and endothelium. Thus antagonism of protease-activated receptor 1 might have broad therapeutic significance. Aprotinin, used clinically to reduce transfusion requirements and the inflammatory response to bypass, has been shown to inhibit protease-activated receptor 1 on platelets in vitro and in vivo. Here we have examined whether aprotinin inhibits endothelial protease-activated receptor 1 activation and resulting proinflammatory responses induced by thrombin.', 'Protease-activated receptor 1 expression and function were examined in cultured human umbilical vein endothelial cells after treatment with alpha-thrombin at 0.02 to 0.15 U/mL in the presence or absence of aprotinin (200-1600 kallikrein inhibitory units/mL). Protease-activated receptor 1 activation was assessed by using an antibody, SPAN-12, which detects only the unactivated receptor, and thrombin-mediated calcium fluxes. Other thrombin-dependent inflammatory pathways investigated were phosphorylation of the p42/44 mitogen-activated protein kinase, upregulation of the early growth response 1 transcription factor, and production of the proinflammatory cytokine interleukin 6.', 'Pretreatment of cultured endothelial cells with aprotinin significantly spared protease-activated receptor 1 receptor cleavage (P < .0001) and abrogated calcium fluxes caused by thrombin. Aprotinin inhibited intracellular signaling through p42/44 mitogen-activated protein kinase (P < .05) and early growth response 1 transcription factor (P < .05), as well as interleukin 6 secretion caused by thrombin (P < .005).\Question: Does aprotinin inhibit proinflammatory activation of endothelial cells by thrombin through the protease-activated receptor 1?

SOLUTION:
This study demonstrates that endothelial cell activation by thrombin and downstream inflammatory responses can be inhibited by aprotinin in vitro through blockade of protease-activated receptor 1. Our results provide a new molecular basis to help explain the anti-inflammatory properties of aprotinin reported clinically.

