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.

[Q]: The antidepressant drug fluoxetine (FLU) is considered in the group of selective serotonine re-uptake inhibitors. Its distribution in brain and binding to human brain glutathione S-transferase- (GST-) have been shown. FLU can cross blood brain barrier and placenta, accumulate in fetus and may cause congenital malformations.', 'To elucidate the interaction of placental GST- with FLU.', 'First, concentration-dependent inhibition of human placental GST- was evaluated by using different FLU concentrations and then 0.3125, 0.625, 1.25, 2.5 and 5mM FLU concentrations were chosen and tested while keeping GSH concentration constant and 1-chloro-2,4-dinitrobenzene (CDNB) concentration varied and vice versa. The data were evaluated with different kinetic models and Statistica 9.00 for Windows.', 'The Vm, at variable [CDNB] (14216U/mg protein) was 3 times higher than the Vm obtained at variable [GSH] (494U/mg protein). On the other hand, the Km for CDNB was 10 times higher than the Km for GSH (1.990.36mM versus 0.210.06mM). The IC50 value for FLU was 8.6mM. Both at constant [CDNB] and variable [GSH] and at constant [GSH] and variable [CDNB] the inhibition types were competitive with the Ki values of 5.624.37 and 8.091.27mM, respectively.
[A]: Does fluoxetine-induced toxicity result in human placental glutathione S-transferase- ( GST- ) dysfunction?

[Q]: Mitochondrial permeability transition pore (mPTP) opening is a terminal event leading to mitochondrial dysfunction and cell death under conditions of oxidative stress (OS). However, mPTP blockade with cyclosporine A (CsA) has shown variable efficacy in limiting post-ischemic dysfunction and arrhythmias. We hypothesized that strong feedback between energy dissipating (mPTP) and cardioprotective (mKATP) channels determine vulnerability to OS.', 'Guinea pig hearts (N = 61) were challenged with H2O2 (200 M) to elicit mitochondrial membrane potential (m) depolarization. High-resolution optical mapping was used to measure m or action potentials (AP) across the intact heart. Hearts were treated with CsA (0.1 M) under conditions that altered the activity of mKATP channels either directly or indirectly via its regulation by protein kinase C. mPTP blockade with CsA markedly blunted (P < 0.01) OS-induced m depolarization and delayed loss of LV pressure (LVP), but did not affect arrhythmia propensity. Surprisingly, prevention of mKATP activation with the chemical phosphatase BDM reversed the protective effect of CsA, paradoxically exacerbating OS-induced m depolarization and accelerating arrhythmia onset in CsA treated compared to untreated hearts (P < 0.05). To elucidate the putative molecular mechanisms, mPTP inhibition by CsA was tested during conditions of selective PKC inhibition or direct mKATP channel activation or blockade. Similar to BDM, the specific PKC inhibitor, CHE (10 M) did not alter OS-induced m depolarization directly. However, it completely abrogated CsA-mediated protection against OS. Direct pharmacological blockade of mKATP, a mitochondrial target of PKC signaling, equally abolished the protective effect of CsA on m depolarization, whereas channel activation with 30 M Diazoxide protected against m depolarization (P < 0.0001). Conditions that prevented mKATP activation either directly or indirectly via PKC inhibition led to accelerated m depolarization and early onset of VF in response to OS. Investigation of the electrophysiological substrate revealed accelerated APD shortening in response to OS in arrhythmia-prone hearts.
[A]: Do functional crosstalk between the mitochondrial PTP and KATP channels determine arrhythmic vulnerability to oxidative stress?

[Q]: The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression.', 'Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies.', 'Immunofluorescent staining revealed TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha-induced TRPA1 responses after Biodentine treatment.
[A]:
Does biodentine reduce Tumor Necrosis Factor Alpha-induced TRPA1 Expression in Odontoblastlike Cells?