Steady states of holographic interfaces

We find stationary thin-brane geometries that are dual to far-from-equilibrium steady states of two-dimensional holographic interfaces. The flow of heat at the boundary agrees with the result of CFT and the known energy-transport coefficients of the thin-brane model. We argue that by entangling outgoing excitations the interface produces thermodynamic entropy at a maximal rate, and point out similarities and differences with double-sided black funnels. The non-compact, non-Killing and far-from-equilibrium event horizon of our solutions coincides with the local (apparent) horizon on the colder side, but lies behind it on the hotter side of the interface. We also show that the thermal conductivity of a pair of interfaces jumps at the Hawking-Page phase transition from a regime described by classical scatterers to a quantum regime in which heat flows unobstructed.

Abstract P405: Cardioprotective Actions Of Nitroxyl Donor Angeli's Salt Are Preserved In The Diabetic Heart And Vasculature In The Face Of Nitric Oxide Resistance

Introduction: The risk of fatal cardiovascular events is increased in patients with type 2 diabetes mellitus (T2DM). A major contributor to poor prognosis is impaired nitric oxide (NO•) signalling at the level of tissue responsiveness, termed NO• resistance. Nitroxyl (HNO) induces positive inotropic and lusitropic effects in healthy and failing hearts. Hypothesis: We hypothesised that in a rodent model, T2DM will promote, and HNO will circumvent, NO• resistance in the myocardium and coronary vasculature. Methods: At 8 weeks of age, male Sprague-Dawley rats commenced a high-fat diet. After two weeks, the rats received low-dose streptozotocin (two intraperitoneal injections, 35 mg/kg, over two consecutive days), and continued the diet. Twelve weeks later, hearts were Langendorff-perfused to assess responses to the NO• donor diethylamine NONOate (DEA/NO) and the HNO donor Angeli’s salt. Results: Inotropic, lusitropic and coronary vasodilator responses to DEA/NO were impaired, and responses to Angeli’s salt were preserved or enhanced, in T2DM hearts compared with non-diabetic hearts. Conclusions: This is the first evidence that inotropic and lusitropic responses are preserved, and NO• resistance in the coronary vasculature is circumvented, by the HNO donor Angeli’s salt in T2DM. These findings highlight the cardiovascular therapeutic potential of HNO donors, especially in cardiac emergencies such as acute ischaemia or heart failure. Figure 1. Dose-response curves and maximal responses to DEA/NO or Angeli's salt in diabetic or non-diabetic hearts. (A-C) LV+dP/dt, (D-F) LV-dP/dt and (G-I) coronary flow rate. Data expressed as change from baseline (denoted by Δ), mean ± SEM. Data analysed by two-way RM ANOVA with Sidak's post-hoc test. *P<0.05 vs. non-diabetic. LV, left ventricular; LV+dP/dt, maximal rate of rise in LV pressure; LV-dP/dt, maximal rate of fall in LV pressure.

Experimental study of non-oxidized and oxidized bitumen obtained from heavy oil

Heavy oil and vacuum residue were used to obtain road bitumen BND 50/70 using two different methods of steam distillation at 323–362 °C and by oxidation, a method using packed column at temperature of 211–220 °C. The obtained residues using two methods steam distillation and oxidation are known as non-oxidized bitumen and oxidized bitumen, respectively. The products were evaluated using different standards including GOST 33133-2014, GOST 22245-90, and ASTM D5. The results showed that the yield of oxidized bitumen reached a maximal rate of 89.59% wt., while that of non-oxidized bitumen is 55% wt. The softening point of oxidized bitumen is 49–57 °C compared to non-oxidized bitumen (46–49 °C). Remarkably, the previous softening point and penetrability of 47–71 points of oxidized bitumen are consistent with norms to BND 50/70 bitumen, according standard. The non-oxidized bitumen has a relatively low softening point and a higher penetration value of 71–275, which refers to BND 200/300 bitumen. Comparatively, the use of a packed column is beneficial than the steam distillation, due to high capability of the nozzles to strengthens contact between feedstock and compressed air in the reaction zone and decreases the reaction time to 4.15 h.

Peripheral-central interplay for fatiguing unresisted repetitive movements: a study using muscle ischaemia and M1 neuromodulation

Maximal-rate rhythmic repetitive movements cannot be sustained for very long, even if unresisted. Peripheral and central mechanisms of fatigue, such as the slowing of muscle relaxation and an increase in M1-GABAb inhibition, act alongside the reduction of maximal execution rates. However, maximal muscle force appears unaffected, and it is unknown whether the increased excitability of M1 GABAergic interneurons is an adaptation to the waning of muscle contractility in these movements. Here, we observed increased M1 GABAb inhibition at the end of 30 s of a maximal-rate finger-tapping (FT) task that caused fatigue and muscle slowdown in a sample of 19 healthy participants. The former recovered a few seconds after FT ended, regardless of whether muscle ischaemia was used to keep the muscle slowed down. Therefore, the increased excitability of M1-GABAb circuits does not appear to be mediated by afferent feedback from the muscle. In the same subjects, continuous (inhibitory) and intermittent (excitatory) theta-burst stimulation (TBS) was used to modulate M1 excitability and to understand the underlying central mechanisms within the motor cortex. The effect produced by TBS on M1 excitability did not affect FT performance. We conclude that fatigue during brief, maximal-rate unresisted repetitive movements has supraspinal components, with origins upstream of the motor cortex.

The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats

ObjectiveThe purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism.MethodsSprague-Dawley (SD) rats (n = 25) were divided into five groups randomly: (1) Sham, (2) I/R, (3) I/R + RSV (10 mg/kg), (4) IR + DGZ (1 mg/kg), and (5) I/R + RSV (10 mg/kg) + DGZ (1 mg/kg). The I/R model was induced with 30 min of left anterior descending occlusion followed by 120 min of reperfusion.ResultsIn vivo pretreatment with RSV and DGZ, respectively, showed a significant reduction of infarction size, a significant increase in the levels of left ventricular systolic pressure, and maximal rate increase in left ventricular pressure (+dp/dtmax), decrease in the levels of left ventricular end-diastolic pressure (LVEDP), maximal rate of decrease of left ventricular pressure (−dp/dtmax) and activity of cardiac enzymes of creatine kinase (CK), creatine kinase MB isoenzymes (CK-MB), and hyper-tensive cardiac troponin I compared with the I/R group. H9C2 cells were exposed to hypoxia/reoxygenation to simulate an I/R model. In vitro administration of 25 µM RSV and 50 µM DGZ significantly enhanced cell viability, upregulated the expression levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2, whereas it downregulated cleaved-caspase3, Bax. TUNEL assay indicated that pretreatment with RSV and DGZ decreased the apoptosis of H9C2 cells.ConclusionThe combination of RSV and DGZ significantly enhances the cardioprotective effects compared with RSV or DGZ alone. RSV and DGZ have the potential cardioprotective effects against I/R injury by activating the PI3K/AKt/mTOR signaling pathway.

Hemoglobin drop following postpartum hemorrhage

Postpartum hemorrhage (PPH) is defined as blood loss of ≥ 500–1000 ml within 24 h after delivery. Yet, assessment of blood loss is imprecise. The present study aimed to profile the hemoglobin (Hb) drop after vaginal delivery with versus without PPH. This was a secondary analysis of a prospective cohort study of women who delivered vaginally. Women were included if complete blood counts (CBC) before and after delivery were taken until stabilization (N = 419). Women were categorized into the PPH group and controls, for whom post-delivery CBCs were performed due to indications unrelated to bleeding. The PPH patients were then classified as either overt or occult PPH (symptoms related to hypovolemia without overt bleeding) subgroups. The primary endpoint was mean Hb drop after delivery. One hundred and ten (26%) and 158 (38%) women presented with overt PPH or occult PPH, respectively; 151 (36%) women were included in the control group. Mean Hb decrease from baseline was 3.0 ± 1.6, 2.0 ± 1.4 and 0.9 ± 1.0 g/dl, respectively (p < 0.0001). In all groups, maximal rate of Hb decline was in the first 6–12 h postpartum and plateaued after 24–48 h. At 48 h post-delivery, 95% and 86% of women who had dropped to Hb ≤ 9.5 and < 7 g/dl, respectively, reached those thresholds. Taken together, an Hb decrease ≥ 2 g/dl was consistent with PPH diagnosis and should be followed for at least 48 h after delivery.

Dependence of the adaptive capacity of liver mitochondria on preparation method

When conducting studies on isolated hepatocytes, it is important to obtain cells that retain the functional properties that are characteristic of the whole organ. Increased blood viscosity during liver perfusion, decreased perfusion pressure in blood vessels, and hence hypoxia, are among the factors that may affect the functional state of isolated hepatocytes. The functional state of cells can be estimated by the adaptive capacity of mitochondria, by inducing maximal respiration rate by uncoupling respiration and oxidative phosphorylation due to the addition of FCCP. The research aimed to investigate the adaptive capacity of mitochondria of isolated hepatocytes using in situ and in vitro liver perfusion. Hepatocytes were isolated by the two-staged Seglen method by in situ and in vitro liver perfusion. Isolated hepatocytes, after 15-minute incubation in the medium without addition or with respective oxidative substrate – glutamine, pyruvate, succinate, monomethyl succinate, α-ketoglutarate, dimethyl-α-ketoglutarate (at a concentration of 2 mM) or glucose (10 mM) – were added into the respiratory chamber and FCCP was added in increasing concentrations. It was established that at in situ liver perfusion maximal rate of uncoupled respiration and the optimal concentration of FCCP was higher than at in vitro liver perfusion. Addition of exogenous substrates to a medium increased the respiration rate of hepatocytes. Upon in situ liver perfusion maximal uncoupled respiration rate increased at all causes except glucose, and at in vitro liver perfusion – only when dimethyl-α-ketoglutarate, succinate and monomethyl succinate were used. The optimal concentration of FCCP at in vitro liver perfusion increased due to the addition of glutamine, pyruvate and monomethyl succinate to the medium, and at in situ liver perfusion – only upon glucose oxidation. In both perfusion methods, the highest maximal rate of uncoupled respiration is with the use of monomethyl succinate and the optimal FCCP concentration – upon pyruvate oxidation. Therefore, in situ liver perfusion is better method to obtain stable and metabolically active hepatocytes in support respiratory processes at a high level then in vitro perfusion.

Cardiac electrophysiological effects of ibuprofen in dog and rabbit ventricular preparations: Possible implication to enhanced proarrhythmic risk

Ibuprofen is a widely used non-steroidal anti-inflammatory drug, which has recently been associated with increased cardiovascular risk, but its electrophysiological effects have not yet been properly studied in isolated cardiac preparations. We studied the effects of ibuprofen on action potential characteristics and several transmembrane ionic currents using the conventional microelectrode technique and the whole-cell configuration of the patch-clamp technique on cardiac preparations and enzymatically isolated ventricular myocytes. In dog (200 µM; n=6) and rabbit (100 µM; n=7) papillary muscles, ibuprofen moderately but significantly prolonged repolarization at 1 Hz stimulation frequency. In dog Purkinje fibers, repolarization was abbreviated, and maximal rate of depolarization was depressed in a frequency-dependent manner. Levofloxacin (40 µM) alone did not alter repolarization, but augmented the ibuprofen-evoked repolarization lengthening in rabbit preparations (n=7). In dog myocytes, ibuprofen (250 µM) did not significantly influence IK1, but decreased the amplitude of Ito and IKr potassium currents by 28.2% (60 mV) and 15.2% (20 mV) respectively. Ibuprofen also depressed INaL and ICa currents by 19.9% and 16.4%. We conclude that ibuprofen seems to be free from effects on AP parameters at lower concentrations. However, at higher concentrations it may alter repolarization reserve, contributing to the observed proarrhythmic risk in patients.