The nitric oxide ISO photocatalytic reactor system: Measurement of NOx removal activity and capacity

Although the NO removal-based air-purification ISO method ISO 22197-1:2007 is well established, its preconditioning requirements mean that only the initial activity of the photocatalyst under test is measured owing to the often-reported, gradual alteration of the surface kinetics for NO oxidation by air through the accumulation of surface HNO3. Herein, we compare the photocatalytic NO removal abilities of a number of different, common TiO2 materials, surface-saturated with photogenerated HNO3, with their behaviours observed during the typical 5 h-long ISO standard test. It is found that all the TiO2 materials studied eventually become largely NO to NO2 converters after sufficient exposure to NO under irradiation (>5 h) due to the accumulation of surface HNO3. The UV exposure time, t*, necessary to reach this HNO3 saturated condition is different for each different catalyst. As a consequence, an alternative preconditioning process for the ISO method is proposed which can be used to provide a more realistic measure of the photocatalytic activity of the underlying material and provide a measure of the NOx removing capacity of the photocatalytic material under test.

Specific role of neuronal nitric-oxide synthase when tethered to the plasma membrane calcium pump in regulating the beta-adrenergic signal in the myocardium

The cardiac neuronal nitric-oxide synthase (nNOS) has been described as a modulator of cardiac contractility. We have demonstrated previously that isoform 4b of the sarcolemmal calcium pump (PMCA4b) binds to nNOS in the heart and that this complex regulates beta-adrenergic signal transmission in vivo. Here, we investigated whether the nNOS-PMCA4b complex serves as a specific signaling modulator in the heart. PMCA4b transgenic mice (PMCA4b-TG) showed a significant reduction in nNOS and total NOS activities as well as in cGMP levels in the heart compared with their wild type (WT) littermates. In contrast, PMCA4b-TG hearts showed an elevation in cAMP levels compared with the WT. Adult cardiomyocytes isolated from PMCA4b-TG mice demonstrated a 3-fold increase in Ser(16) phospholamban (PLB) phosphorylation as well as Ser(22) and Ser(23) cardiac troponin I (cTnI) phosphorylation at base line compared with the WT. In addition, the relative induction of PLB phosphorylation and cTnI phosphorylation following isoproterenol treatment was severely reduced in PMCA4b-TG myocytes, explaining the blunted physiological response to the beta-adrenergic stimulation. In keeping with the data from the transgenic animals, neonatal rat cardiomyocytes overexpressing PMCA4b showed a significant reduction in nitric oxide and cGMP levels. This was accompanied by an increase in cAMP levels, which led to an increase in both PLB and cTnI phosphorylation at base line. Elevated cAMP levels were likely due to the modulation of cardiac phosphodiesterase, which determined the balance between cGMP and cAMP following PMCA4b overexpression. In conclusion, these results showed that the nNOS-PMCA4b complex regulates contractility via cAMP and phosphorylation of both PLB and cTnI.

Wavelet entropy of Doppler ultrasound blood velocity flow waveforms distinguishes nitric oxide-modulated states

Wavelet entropy assesses the degree of order or disorder in signals and presents this complex information in a simple metric. Relative wavelet entropy assesses the similarity between the spectral distributions of two signals, again in a simple metric. Wavelet entropy is therefore potentially a very attractive tool for waveform analysis. The ability of this method to track the effects of pharmacologic modulation of vascular function on Doppler blood velocity waveforms was assessed. Waveforms were captured from ophthalmic arteries of 10 healthy subjects at baseline, after the administration of glyceryl trinitrate (GTN) and after two doses of N(G)-nitro-L-arginine-methyl ester (L-NAME) to produce vasodilation and vasoconstriction, respectively. Wavelet entropy had a tendency to decrease from baseline in response to GTN, but significantly increased after the administration of L-NAME (mean: 1.60 ± 0.07 after 0.25 mg/kg and 1.72 ± 0.13 after 0.5 mg/kg vs. 1.50 ± 0.10 at baseline, p < 0.05). Relative wavelet entropy had a spectral distribution from increasing doses of L-NAME comparable to baseline, 0.07 ± 0.04 and 0.08 ± 0.03, respectively, whereas GTN had the most dissimilar spectral distribution compared with baseline (0.17 ± 0.08, p = 0.002). Wavelet entropy can detect subtle changes in Doppler blood velocity waveform structure in response to nitric-oxide-mediated changes in arteriolar smooth muscle tone.

Vasoactivity of Rucaparib, a PARP-1 Inhibitor, is a Complex Process that Involves Myosin Light Chain Kinase, P2 Receptors, and PARP Itself

Therapeutic inhibition of poly(ADP-ribose) polymerase (PARP), as monotherapy or to supplement the potencies of other agents, is a promising strategy in cancer treatment. We previously reported that the first PARP inhibitor to enter clinical trial, rucaparib (AG014699), induced vasodilation in vivo in xenografts, potentiating response to temozolomide. We now report that rucaparib inhibits the activity of the muscle contraction mediator myosin light chain kinase (MLCK) 10-fold more potently than its commercially available inhibitor ML-9. Moreover, rucaparib produces additive relaxation above the maximal degree achievable with ML-9, suggesting that MLCK inhibition is not solely responsible for dilation. Inhibition of nitric oxide synthesis using L-NMMA also failed to impact rucaparib's activity. Rucaparib contains the nicotinamide pharmacophore, suggesting it may inhibit other NAD+-dependent processes. NAD+ exerts P2 purinergic receptor-dependent inhibition of smooth muscle contraction. Indiscriminate blockade of the P2 purinergic receptors with suramin abrogated rucaparib-induced vasodilation in rat arterial tissue without affecting ML-9-evoked dilation, although the specific receptor subtypes responsible have not been unequivocally identified. Furthermore, dorsal window chamber and real time tumor vessel perfusion analyses in PARP-1-/- mice indicate a potential role for PARP in dilation of tumor-recruited vessels. Finally, rucaparib provoked relaxation in 70% of patient-derived tumor-associated vessels. These data provide tantalising evidence of the complexity of the mechanism underlying rucaparib-mediated vasodilation.

Chemically blockable transformation and ultraselective low-pressure gas adsorption in a non-porous metal organic framework

Metal organic frameworks (MOFs) are among the most exciting materials discovered recently, attracting particular attention for their gas-adsorption and -storage properties. Certain MOFs show considerable structural flexibility in response to various stimuli. Although there are several examples of 'breathing' MOFs, in which structural changes occur without any bond breaking, examples of transformations in which several bonds are broken and made are much rarer. In this paper we demonstrate how a flexible MOF, Cu-2(OH)(C8H3O7S)(H2O)center dot 2H(2)O, can be synthesized by careful choice of the organic linker ligand. The flexibility can be controlled by addition of a supplementary coordinating molecule, which increases the thermal stability of the solid sufficiently for direct imaging with electron microscopy to be possible. We also demonstrate that the MOF shows unprecedented low-pressure selectivity towards nitric oxide through a coordination-driven gating mechanism. The chemical control over these behaviours offers new possibilities for the synthesis of MOFs with unusual and potentially exploitable properties.