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.

Input: Consider Input: Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further elucidate the mechanisms responsible for reverse rate-dependent drug effects.', 'Action potentials were recorded from multicellular canine ventricular preparations and isolated cardiomyocytes, at cycle lengths (CLs) varying from 0.3 to 5 s, using conventional sharp microelectrodes. APD was either modified by applying inward and outward current pulses, or by superfusion of agents known to lengthen and shorten APD. Net membrane current (I(m)) was calculated from action potential waveforms. The hypothesis that RRD may be implicit in the relationship between I(m) and APD was tested by numerical modelling. Both drug-induced lengthening (by veratrine, BAY-K 8644, dofetilide, and BaCl(2)) and shortening (by lidocaine and nicorandil) of action potentials displayed RRD, i.e. changes in APD were greater at longer than at shorter CL. A similar dependency of effect on CL was found when repolarization was modified by injection of inward or outward current pulses. I(m) measured at various points during repolarization was inversely proportional to APD and to CL. Model simulations showed that RRD is expected as a consequence of the non-linearity of the relationship between I(m) and APD.

Output: Is reverse rate dependency an intrinsic property of canine cardiac preparations?


Input: Consider Input: Post-hemorrhagic shock mesenteric lymph (PHSML) has been linked with neutrophil (PMN) priming, endothelial cell (EC) activation, and acute lung injury (ALI) in rodent models. We have previously identified the lipid fraction of PHSML as containing the causative agent(s). Due to the lesson learned from the rodent gut bacterial translocation experience, we sought to confirm this phenomenon using a large animal model; hypothesizing that lymph collected from the porcine gut following ischemia/reperfusion (I/R) would cause PMN priming.', 'Mesenteric lymph was collected from adult pigs before, during, and for 2 hours after non-lethal hemorrhagic shock (mean arterial pressure = 30 mm Hg x 45 minutes). Whole lymph and the extracted lipid fractions of the lymph were then added to isolated human and porcine PMNs and superoxide production was measured by cytochrome C reduction.', 'Hemorrhagic shock profoundly affected mesenteric lymph flow from baseline (pre-shock) flow rates of 75.63 +/- 8.86 mL/hr to 49.38 +/- 5.76 mL/hr during shock and increasing to 253.38 +/- 27.62 mL/hr after 2 hours of resuscitation. Human PMNs exposed to both whole lymph (PHSML) and its extracted lipids (PHSML Lipid) collected 2 hours after shock exhibited more than a two-fold increase in superoxide release upon activation compared with pre-shock samples: PHSML- 6.27 +/- 0.83 versus 2.56 +/- 0.60 nmolO2(-)/ 3.75 cells/mL/min, respectively (p = 0.007), PHSML Lipid- 4.93 +/- 0.34 versus 2.49 +/- 0.11 nmolO2(-)/ 3.75 cells/mL/min (p < 0.001). Similarly, porcine PMNs exhibited close to a two-fold activation when exposed to the lymph and lipid fraction: PHSML- 4.51 +/- 0.42 versus 1.06 +/- 0.28 nmolO2(-)/ 3.75 cells/mL/min (p = 0.008), PHSML Lipid-4.80 +/- 0.81 versus 1.55 +/- 0.23 nmolO2(-)/ 3.75 cells/mL/min (p = 0.002).

Output: Does systemic neutrophil priming by lipid mediators in post-shock mesenteric lymph exist across species?


Input: Consider Input: Macroprolactinemia is a frequent finding in hyperprolactinemic individuals, usually without clinical impact. Data on biological activity of macroprolactin (bbPRL) are controversial and mostly based on a heterologous rat Nb2 cell bioassay. Biological activity of bbPRL observed in vitro but not in vivo may be due to its high molecular weight, preventing its passage through capillary barrier. Alternatively, bbPRL bioactivity may differ depending on the prolactin (PRL) receptor (PRLR) species specificity.', 'The objective of the study was to characterize the bioactivity of bbPRL in a homologous bioassay: Ba/F-3 cells stably expressing the human PRLR.', "Chromatography-purified bbPRL from macroprolactinemic individuals (group I, n = 18) and monomeric PRL from hyperprolactinemic patients without macroprolactinemia (group II, n = 5) were tested in Nb2 and Ba/F-LLP bioassays. Both groups were followed up at the neuroendocrinology outpatients' clinic.", 'Biological activity of bbPRL presented in the two bioassays was measured.', 'In group I, no patient had hypogonadism. Mean ratio bioactivity to immunoactivity of bbPRL in the Nb2 assay was 0.69. There was no dose-response in 15 of the 18 samples tested in Ba/F-LLP assay. In group II, three patients had galactorrhea and all five had hypogonadism. Mean ratio bioactivity to immunoactivity of monomeric PRL samples was 1.35 in Nb2 and 0.91 in Ba/F-LLP assay.


Output: Does human macroprolactin display low biological activity via its homologous receptor in a new sensitive bioassay?