Conditional pharmacology/toxicology V: ambivalent effects of thiocyanate upon the development and the inhibition of experimental arthritis in rats by aurothiomalate (Myocrysin(R)) and metallic silver

This article discusses the bizarre and contrary effects of thiocyanate, the major detoxication product of hydrogen cyanide inhaled from tobacco smoke or liberated from cyanogenic foods, e.g. cassava. Thiocyanate both (1) promotes inflammatory disease in rats and (2) facilitates the anti-inflammatory action of historic metal therapies based on gold (Au) or silver (Ag) in three models of chronic polyarthritis in rats. Low doses of nanoparticulate metallic silver (NMS) preparations, i.e. zerovalent silver (Ag) administered orally, suppressed the mycobacterial ('adjuvant')-induced arthritis (MIA) in rats. Similar doses of cationic silver, Ag(I), administered orally as silver oxide or soluble silver salts were inactive. By contrast, NMS only inhibited the development of the collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rats when thiocyanate was also co-administered in drinking water. These (a) arthritis-selective and (b) thiocyanate-inducible effects of Ag were also observed in some previous, and now extended, studies with the classic anti-arthritic drug, sodium aurothiomalate (ATM, Myocrisin®) and its silver analogue (STM), administered subcutaneously to rats developing the same three forms of polyarthritis. In the absence of either Ag or ATM, thiocyanate considerably increased the severity of the MIA, CIA and PIA, i.e. acting as a pro-pathogen. Hitherto, thiocyanate was considered relatively harmless. This may not be true in rats/people with immuno-inflammatory stress and concomitant leukocyte activation. Collectively, these findings show how the drug action of a xenobiotic might be determined by the nature (and severity) of the experimental inflammation, as an example of conditional pharmacology. They also suggest that an incipient toxicity, even of normobiotics such as thiocyanate, might likewise be modulated beneficially by well-chosen xenobiotics (drugs, nutritional supplements, etc.), i.e. conditional toxicology (Powanda 1995). Thus, both the disease and the environment may determine (1) the therapeutic action and/or (2) adverse effect(s) of xenobiotics - and even some normobiotics

Galaxy growth in a massive halo in the first billion years of cosmic history

According to the current understanding of cosmic structure formation, the precursors of the most massive structures in the Universe began to form shortly after the Big Bang, in regions corresponding to the largest fluctuations in the cosmic density field(1-3). Observing these structures during their period of active growth and assembly-the first few hundred million years of the Universe-is challenging because it requires surveys that are sensitive enough to detect the distant galaxies that act as signposts for these structures and wide enough to capture the rarest objects. As a result, very few such objects have been detected so far(4,5). Here we report observations of a far-infrared-luminous object at redshift 6.900 (less than 800 million years after the Big Bang) that was discovered in a wide-field survey(6). High-resolution imaging shows it to be a pair of extremely massive star-forming galaxies. The larger is forming stars at a rate of 2,900 solar masses per year, contains 270 billion solar masses of gas and 2.5 billion solar masses of dust, and is more massive than any other known object at a redshift of more than 6. Its rapid star formation is probably triggered by its companion galaxy at a projected separation of 8 kiloparsecs. This merging companion hosts 35 billion solar masses of stars and has a star-formation rate of 540 solar masses per year, but has an order of magnitude less gas and dust than its neighbour and physical conditions akin to those observed in lower-metallicity galaxies in the nearby Universe(7). These objects suggest the presence of a dark-matter halo with a mass of more than 100 billion solar masses, making it among the rarest dark-matter haloes that should exist in the Universe at this epoch

A massive core for a cluster of galaxies at a redshift of 4.3

Massive galaxy clusters are now found as early as 3 billion years after the Big Bang, containing stars that formed at even earlier epochs. The high-redshift progenitors of these galaxy clusters, termed 'protoclusters', are identified in cosmological simulations with the highest dark matter overdensities. While their observational signatures are less well defined compared to virialized clusters with a substantial hot intra-cluster medium (ICM), protoclusters are expected to contain extremely massive galaxies that can be observed as luminous starbursts. Recent claimed detections of protoclusters hosting such starbursts do not support the kind of rapid cluster core formation expected in simulations because these structures contain only a handful of starbursting galaxies spread throughout a broad structure, with poor evidence for eventual collapse into a protocluster. Here we report that the source SPT2349-56 consists of at least 14 gas-rich galaxies all lying at z = 4.31 based on sensitive observations of carbon monoxide and ionized carbon. We demonstrate that each of these galaxies is forming stars between 50 and 1000 times faster than our own Milky Way, and all are located within a projected region only $\sim$ 130 kiloparsecs in diameter. This galaxy surface density is more than 10 times the average blank field value (integrated over all redshifts) and $>$1000 times the average field volume density. The velocity dispersion ($\sim$ 410 km s$^{-1}$) of these galaxies and enormous gas and star formation densities suggest that this system represents a galaxy cluster core at an advanced stage of formation when the Universe was only 1.4 billion years old. A comparison with other known protoclusters at high redshifts shows that SPT2349-56 is a uniquely massive and dense system that could be building one of the most massive structures in the Universe today.Comment: To appear in April 26 issue of Natur