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The efficacy and safety of romiplostim, a thrombopoietin-mimetic peptibody, were evaluated in a double-blind, placebo-controlled, randomized trial of Japanese patients with chronic immune thrombocytopenia (ITP). Thirty-four ITP patients received romiplostim (n = 22) or placebo (n = 12) for 12 weeks, with a starting romiplostim dose of 3 μg/kg weekly. The primary end point was the number of weeks with platelet response, defined as a platelet count ≥50 × 10(9)/L (not including the 4 weeks after rescue medication administration). Patients received a median of 4 (range 1-19) prior ITP therapies including splenectomy in 44%. On study, 68% also received concomitant ITP therapy. Weekly responses occurred for a median of 11 weeks with romiplostim as compared to 0 weeks with placebo (p < 0.0001). Most romiplostim-treated patients (95%) achieved platelet responses; two showed extended responses after the treatment period. The use of rescue medication was required in 9% of romiplostim-treated patients as compared with 17% of placebo-treated patients. Both treatment groups had similar incidences of adverse events (91% romiplostim, 92% placebo). Adverse events that occurred more frequently (>10%) in romiplostim-treated patients included nasopharyngitis, headache, peripheral edema, back pain, and extremity pain. In conclusion, romiplostim significantly increased and maintained platelet counts and was well tolerated in Japanese patients with ITP.

Even under anisotonic conditions, most cells can regulate their volume by mechanisms called regulatory volume decrease (RVD) and increase (RVI) after osmotic swelling or shrinkage, respectively. In contrast, the initial processes of necrosis and apoptosis are associated with persistent swelling and shrinkage. Necrotic volume increase (NVI) is initiated by uptake of osmolytes, such as Na + , Cl − and lactate, under conditions of injury, hypoxia, ischaemia, acidosis or lactacidosis. Persistence of NVI is caused by dysfunction of RVD due to impairment of volume-sensitive Cl − channels under conditions of ATP deficiency or lactacidosis. Both lactacidosis-induced RVD dysfunction and necrotic cell death are prevented by pretreatment of cells with the vacuolating cytotoxin-A (VacA) toxin protein purified from Helicobacter pylori, which forms a lactacidosis-resistant anion channel. Apoptotic volume decrease (AVD) is triggered by activation of K + and Cl − conductances following stimulation with a mitochondrion-mediated or death receptor-mediated apoptosis inducer. Apoptotic cell death can be prevented by blocking the Cl − channels but not the K + -Cl − cotransporters. Thus, the volume regulatory anion channel plays, unless impaired, a cell-rescuing role in the necrotic process by ensuring RVD after swelling induced by necrotic insults, whereas normotonic activation of the anion channel plays a cell-killing role in the apoptotic process by triggering AVD following stimulation with apoptosis inducers.

Oberflächenanalyse: Mittels In‐situ‐Totalreflexions‐Röntgenfluoreszenz‐Absorptionsspektroskopie wurde gefunden, dass Cobalt an der Oberfläche einer LiCoO2‐Elektrode vom flüssigen Elektrolyten reduziert wird. Ein irreversibles Verhalten wurde an der LiCoO2‐Oberfläche während des ersten Lade‐/Entladeprozesses beobachtet, wohingegen das Bulk‐Material ein reversibles Verhalten zeigte. Die Cobalt‐Reduktion ist Auslöser für den Abbau der Elektrode.

Because persistent swelling causes cell damage and often results in cell death, volume regulation is an important physiological function in both neuronal and non-neuronal cells. Brain cell swelling has been observed not only in various pathological conditions but also during physiological synaptic transmissions. Volume-sensitive anion channels have been reported to play an important role in the regulatory volume decrease occurring after osmotic swelling in many cell types. In this study, using a two-photon laser scanning microscope and patch-clamp techniques, we found that mouse cortical neurons in primary culture exhibit regulatory volume decrease after transient swelling and activation of Cl- currents during exposure to a hypotonic solution. The regulatory volume decrease was inhibited by Cl- channel blockers or K+ channel blockers. Swelling-activated Cl- currents exhibited outward rectification, time-dependent inactivation at large positive potentials, a low-field anion permeability sequence, an intermediate unitary conductance and sensitivity to known blockers of volume-sensitive Cl- channels. Thus, it is concluded that the activity of the volume-sensitive outwardly rectifying Cl- channel plays a role in the control of cell volume in cortical neurons.

Pluripotent hemopoietic stem cells (P-HSCs) were thought to be c-kit ؉ , but recent reports indicate that they are c-kit low . In the present report, we provide evidence using Ly5 congenic mice that P-HSCs are c-kit

For the further development of lithium-ion batteries, improvement of their cyclic performance is crucial. However, the mechanism underlying the deterioration of the battery cyclic performance is not fully understood. We investigated the effects of the electronic structure at the electrode/electrolyte interface on the cyclic performance of the cathode materials via in situ total-reflection fluorescence X-ray absorption spectroscopy. In a LiCoO2 thin-film electrode that exhibits gradual deterioration upon subsequent Li ion extractions and insertions (cycling), the reduction of Co ions at the electrode/electrolyte interface was observed upon immersion in an organic electrolyte, with subsequent irreversible changes after cycling. In contrast, in a LiFePO4 thin-film electrode, the electronic structure at the electrode/electrolyte interface was stable and reversible upon electrolyte immersion with subsequent cycling. The increased stability of the electronic structure at the LiFePO4/electrolyte interface affects its cycling performance.

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