instruction:
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.
question:
We hypothesized that erythropoietin (EPO)-immersed gelatin hydrogel microspheres (GHM) injected into ischemic legs might continuously release a small amount of EPO to locally stimulate angiogenesis without unfavorable systemic effects.', 'EPO is a potent angiogenic factor, but its use for relieving ischemic organs is limited because of the untoward systemic erythrogenic effect and its short half-life in plasma.', 'The right femoral arteries of BALB/c mice were ligated. Recombinant human EPO (5,000 IU/kg)-immersed GHM was injected into the right hind limb muscles (n = 12); the control groups included a saline-injected group (n = 12), an EPO-injected group (n = 8), and an empty GHM-injected group (n = 8).', 'Eight weeks later, improvement of blood perfusion to the ischemic limb was significantly augmented in the EPO-GHM group compared with any of the control groups. There was no increase in the hemoglobin level, nor was there any increase in endothelial progenitor cells. However, capillary and arteriolar densities were significantly increased in this group. Although the treatment did not affect the levels of vascular endothelial growth factor or interleukin-1 beta, it up-regulated the EPO receptor and matrix metalloproteinase-2 and activated the downstream signaling of Akt and also endothelial nitric oxide synthase in ischemic limbs, which might have been associated with the evident angiogenic and arteriogenic effects in the present system.
answer:
Does sustained release of erythropoietin using biodegradable gelatin hydrogel microspheres persistently improve lower leg ischemia?

question:
Angiotensin II (Ang II) signaling has been implicated in cardiac arrhythmogenesis, which involves induction of reactive oxygen species (ROS). It was shown that Ang II can activate Ca/Calmodulin kinase II (CaMKII) by oxidation via a NADPH oxidase 2 (NOX2)-dependent pathway leading to increased arrhythmic afterdepolarizations. Interestingly, cAMP-dependent protein kinase A (PKA) which regulates similar targets as CaMKII has recently been shown to be redox-sensitive as well.', 'This study aims to investigate the distinct molecular mechanisms underlying Ang II-related cardiac arrhythmias with an emphasis on the individual contribution of PKA vs. CaMKII.', 'Isolated ventricular cardiac myocytes from rats and mice were used. Ang II exposure resulted in increased NOX2-dependent ROS generation assessed by expression of redox-sensitive GFP and in myocytes loaded with ROS indicator MitoSOX. Whole cell patch clamp measurements showed that Ang II significantly increased peak Ca and Na current (ICa and INa) possibly by enhancing steady-state activation of ICa and INa. These effects were absent in myocytes lacking functional NOX2 (gp91phox(-/-)). In parallel experiments using PKA inhibitor H89, the Ang II effects on peak INa and ICa were also absent. In contrast, genetic knockout of CaMKII (CaMKII(-/-)) did not influence the Ang II-dependent increase in peak ICa and INa. On the other hand, Ang II enhanced INa inactivation, increased late INa and induced diastolic SR (sarcoplasmic reticulum) Ca leak (confocal Ca spark measurements) in a CaMKII-, but not PKA-dependent manner. Surprisingly, only the increase in diastolic SR Ca leak was absent in gp91phox(-/-)myocytes suggesting that Ang II regulates INa inactivation in a manner dependent on CaMKII- but not on NOX2. Finally, we show that Ang II increased the propensity for cellular arrhythmias, for which PKA and CaMKII contribute, both dependent on NOX2.
answer:
Does nADPH oxidase 2 mediate angiotensin II-dependent cellular arrhythmias via PKA and CaMKII?

question:
Various techniques and devices have been proposed for tricuspid valve (TV) repair in patients with tricuspid regurgitation (TR). However, residual or recurrent TR is not uncommon occurring in 20% to 30% of patients. This study reports first experiences with a new three-dimensional annuloplasty ring.', 'We retrospectively reviewed 200 consecutive patients who underwent TV repair for functional TR with the Contour 3D annuloplasty ring (Medtronic, Minneapolis, MN) from December 2010 to February 2013 at our institution. The follow-up is 98% complete (mean 1.0 0.7 years; cumulative total 189 patient-years).', 'Mean age was 70.4 9.1 years and the median logistic European system for cardiac operative risk was 7%. Sixty-nine percent of the patients were in New York Heart Association class III/IV. Echocardiography documented moderate or severe TR in 97.5% of the patients, with a mean annulus diameter of 45.1 4.9 mm; 93.5% of the patients underwent a combined procedure, and 20.5% an urgent or emergent operation. The 30-day mortality was 6%. The preoperative TR grade was reduced from 2.45 0.53 to 0.77 0.54 (p < 0.001). At hospital discharge residual II TR or greater was present in 4.3% of the patients. Freedom from recurrent II TR or greater at 2years was 90.9% 4.2% and freedom from TV-related reoperations at 2 years was 98.5% 1.0%. No case ofring dehiscence occurred. Fourteen patients (7%) required a permanent pacemaker implantation for atrioventricular block.
answer:
Does early experience with a new three-dimensional annuloplasty ring for the treatment of functional tricuspid regurgitation?