TASK DEFINITION: Given a passage, 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: Apelin has been shown ex vivo to be a potent cardiac inotrope. This study was undertaken to evaluate the in vivo effects of apelin on cardiac function in native and ischemic cardiomyopathic rat hearts using a novel combination of a perivascular flow probe and a conductance catheter.', 'Native rats (n =32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n =22) underwent median sternotomy with placement of a perivascular flow probe around the ascending aorta and a pressure volume conductance catheter into the left ventricle. Compared with sham-operated rats, the ligated rats had significantly decreased baseline Pmax and max dP/dt. Continuous infusion of apelin at a rate of 0.01 microg/min for 20 minutes significantly increased Pmax and max dP/dt compared with infusion of vehicle alone in both native and failing hearts. Apelin infusion increased cardiac contractility, indicated by a significant increase in stroke volume (SV) without a change in left ventricular end diastolic volume (102+/-16% change from initial SV versus 26+/-20% for native animals, and 110+/-30% versus 26+/-11% for ligated animals), as well as an increase in preload recruitable stroke work (180+/-24 mm Hg versus 107+/-9 mm Hg for native animals).

SOLUTION: Does apelin have in vivo inotropic effects on normal and failing hearts?

PROBLEM: Normal glucose metabolism depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilisation, glucagon excess is the principal factor in diabetic glucose overproduction. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance.', 'Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metabolism was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist.', 'Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass.

SOLUTION: Does acute disruption of glucagon secretion or action improve glucose tolerance in an insulin-deficient mouse model of diabetes?

PROBLEM: The putative role of sulfur amino acids such as homocysteine (tHcy) as cardiovascular risk factors is controversial in chronic kidney disease (CKD). Although, S-adenosylhomocysteine (SAH) levels have been linked to CVD in non-renal populations, such relationship has not been evaluated in CKD.', 'Serum concentrations of S-adenosylmethionine (SAM), SAH and total homocysteine (tHcy) were determined by HPLC in 124 CKD stage 5 patients (GFR range 1-11 m/min) and 47 control subjects, and related to renal function, presence of CVD, inflammation and protein-energy wasting (PEW).', 'The levels of SAM and SAH were higher in CKD patients than in controls. Both SAM (rho=-0.19; P<0.05) and SAH (rho=-0.37, P<0.001) were inversely related to GFR. The concentrations of SAH were significantly higher (P<0.001) in patients with CVD than in non-CVD patients, (683 (201-3057) vs 485 (259-2620) nmol/L; median (range)) as opposed to tHcy levels, which were lower in CVD patients. While SAH was not associated with the presence of inflammation or PEW, it was a significant contributor (OR; 4.9 (CI 1.8-12.8), P<0.001) to CVD in a multinomial logistic regression model (pseudo r(2)=0.31).

SOLUTION:
Are elevated serum levels of S-adenosylhomocysteine , but not homocysteine , associated with cardiovascular disease in stage 5 chronic kidney disease patients?