Stability of methylnicotinate in aqueous solution as utilized in the 'niacin patch test'

<p>Abstract</p> <p>Background</p> <p>The topical application of methylnicotinate results in a localized vasodilatatory response which has been found to differ from that observed to occur in healthy controls in a variety of medical conditions. The stability of the drug in aqueous solution is unclear while difficulties can be encountered when preparing methylnicotinate solutions for this purpose. To aid in the determination of how long solutions of the drug should be stored before discarding we have used a collection of aged batches of methylnicotinate to determine the stability of the drug in aqueous solution.</p> <p>Findings</p> <p>The degradation of methylnicotinate was determined in batches which had been stored at 4°C for between 5 and 1062 days prior to analysis by High Performance Liquid Chromatography. The major degradation product of methylnicotinate was nicotinic acid which formed at an approximate rate of 0.5% of the starting methylnicotinate concentration per annum. Furthermore, the ability of methylnicotinate solutions of different ages to induce vasodilatation was assessed in healthy volunteers. No significant difference in vasodilatatory response was apparent between batches which had been stored for between zero and 1057 days.</p> <p>Conclusion</p> <p>Methylnicotinate exhibits excellent chemical and biological stability in solution facilitating its use in clinical applications.</p

Low Temperature Photo-oxidation of Chloroperoxidase Compound II

Oxidation of the heme-thiolate enzyme chloroperoxidase (CPO) from Caldariomyces fumago with peroxynitrite (PN) gave the Compound II intermediate, which was photo-oxidized with 365 nm light to give a reactive oxidizing species. Cryo-solvents at pH ≈ 6 were employed, and reactions were conducted at temperatures as low as − 50 °C. The activity of CPO as evaluated by the chlorodimedone assay was unaltered by treatment with PN or by production of the oxidizing transient and subsequent reaction with styrene. EPR spectra at 77 K gave the amount of ferric protein at each stage in the reaction sequence. The PN oxidation step gave a 6:1 mixture of Compound II and ferric CPO, the photolysis step gave an approximate 1:1 mixture of active oxidant and ferric CPO, and the final mixture after reaction with excess styrene contained ferric CPO in 80% yield. In single turnover reactions at − 50 °C, styrene was oxidized to styrene oxide in high yield. Kinetic studies of styrene oxidation at − 50 °C displayed saturation kinetics with an equilibrium constant for formation of the complex of Kbind = 3.8 × 104 M− 1 and an oxidation rate constant of kox = 0.30 s− 1. UV–Visible spectra of mixtures formed in the photo-oxidation sequence at ca. − 50 °C did not contain the signature Q-band absorbance at 690 nm ascribed to CPO Compound I prepared by chemical oxidation of the enzyme, indicating that different species were formed in the chemical oxidation and the photo-oxidation sequence

SWAS observations of comet 9P/Tempel 1 and Deep Impact

On 4 July 2005 at 1:52 UT the Deep Impact mission successfully completed its goal to hit the nucleus of 9P/Tempel 1 with an impactor, forming a crater on the nucleus and ejecting material into the coma of the comet. The 370 kg impactor collided with the sunlit side of the nucleus with a relative velocity of 10.2 km/s. NASA's Submillimeter Wave Astronomy Satellite (SWAS) observed the 1(10)-1(01) ortho-water ground-state rotational transition in comet 9P/Tempel 1 before, during, and after the impact. No excess emission from the impact was detected by SWAS. However, the water production rate of the comet showed large natural variations of more than a factor of three during the weeks before the impact.Comment: to appear in the proceedings of the IAU Symposium No. 231: "Astrochemistry - Recent Successes and Current Callenges". Typo corrected in author affiliation lis

The preparation and characterisation of monomeric and linked metal carbonyl clusters containing the closo-Si2Co4 pseudo-octahedral core

PhSiH3 reacts with [Co₄(CO)₁₂] at 50 °C in hydrocarbon solvents to give [(µ₄-SiPh)₂Co₄(CO)₁₁], 2c, shown by an X-ray crystal structure determination to have a pseudo-octahedral Si₂Co₄ core. Substituted aryl-silanes behaved similarly. Mixtures of PhSiH₃, H₃SiC₆H₄SiH₃ and [Co₄(CO)₁₂] in a ca. 2 1 2 ratio gave the dimeric cluster [{Co₄(µ₄-SiPh)(CO)₁₁Si}₂C₆H₄], 3a, which has the two Si₂Co₄ cores linked by a C₆H₄ group to give a rigid molecule which an X-ray structure analysis shows to be over 23 Å long. Related dimers linked by –(CH₂)₈– groups were isolated from mixtures of PhSiH₃, α ,ω-(H₃Si)₂(CH₂)₈ and [Co₄(CO)₁₂]. Electrochemical studies show the two cluster units in 3a do not interact electronically

Short communication: NKG2C+ NK cells contribute to increases in CD16+CD56- cells in HIV type 1+ individuals with high plasma viral load.

Chronic HIV-1 infection results in the expansion of both NKG2C+ and CD16+CD56- human natural killer cells. NKG2C+ cells proliferate in response to human cytomegalovirus (HCMV) and expansion of the dysfunctional CD56-CD16+ natural killer (NK) cells is associated with HIV-1 viremia. Here we report an association between increased proportions of CD56-CD16+ NK cells in viremic HIV-1+ individuals and an increased contribution of NKG2C+ cells to this subset. These data, in addition to anti-HCMV IgG serology, indicate a potential contribution of both HCMV and HIV-1 to NK cell dysfunction in HIV-1-infected individuals

Looming struggles over technology for border control

New technologies under development, capable of inflicting pain on masses of people, could be used for border control against asylum seekers. Implementation might be rationalized by the threat of mass migration due to climate change, nuclear disaster or exaggerated fears of refugees created by governments. We focus on taser anti-personnel mines, suggesting both technological countermeasures and ways of making the use of such technology politically counterproductive. We also outline several other types of ‘non-lethal’ technology that could be used for border control and raise human rights concerns: high-powered microwaves, armed robots, wireless tasers, acoustic devices/vortex rings, ionizing and pulsed energy lasers, chemical calmatives, convulsants, bioregulators and malodurants. Whether all these possible border technologies will be implemented is a matter for speculation, but their serious human rights implications warrant advance scrutiny

Voltage-Controlled Optics of a Quantum Dot

We show how the optical properties of a single semiconductor quantum dot can be controlled with a small dc voltage applied to a gate electrode. We find that the transmission spectrum of the neutral exciton exhibits two narrow lines with $\sim 2$ $\mu$eV linewidth. The splitting into two linearly polarized components arises through an exchange interaction within the exciton. The exchange interaction can be turned off by choosing a gate voltage where the dot is occupied with an additional electron. Saturation spectroscopy demonstrates that the neutral exciton behaves as a two-level system. Our experiments show that the remaining problem for manipulating excitonic quantum states in this system is spectral fluctuation on a $\mu$eV energy scale.Comment: 4 pages, 4 figures; content as publishe