Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections

Colonisation of the gastrointestinal tract by anaerobic bacteria, protozoa, trematodes, cestodes and/or nematodes and other infectious pathogens, including viruses, represents a major cause of morbidity and mortality in Africa, South America and southeast Asia, as well as other parts of the world. Nitazoxanide is a member of the thiazolide class of drugs with a documented broad spectrum of activity against parasites and anaerobic bacteria. Moreover, the drug has recently been reported to have a profound activity against hepatitis C virus infection. In addition, nitazoxanide exhibits anti-inflammatory properties, which have prompted clinical investigations for its use in Crohn's disease. Studies with nitazoxanide derivatives have determined that there must be significantly different mechanisms of action acting on intracellular versus extracellular pathogens. An impressive number of clinical studies have shown that the drug has an excellent bioavailability in the gastrointestinal tract, is fast acting and highly effective against gastrointestinal bacteria, protozoa and helminthes. A recent Phase II study has demonstrated viral response (hepatitis C) to monotherapy, with a low toxicity and an excellent safety profile over 24 weeks of treatment. Pre-clinical studies have indicated that there is a potential for application of this drug against other diseases, not primarily affecting the liver or the gastrointestinal tract.

Laboratory observations and simulations of phase reddening

The visible reflectance spectrum of many Solar System bodies changes with changing viewing geometry for reasons not fully understood. It is often observed to redden (increasing spectral slope) with increasing solar phase angle, an effect known as phase reddening. Only once, in an observation of the martian surface by the Viking 1 lander, was reddening observed up to a certain phase angle with bluing beyond, making the reflectance ratio as a function of phase angle shaped like an arch. However, in laboratory experiments this arch-shape is frequently encountered. To investigate this, we measured the bidirectional reflectance of particulate samples of several common rock types in the 400–1000 nm wavelength range and performed ray-tracing simulations. We confirm the occurrence of the arch for surfaces that are forward scattering, i.e. are composed of semi-transparent particles and are smooth on the scale of the particles, and for which the reflectance increases from the lower to the higher wavelength in the reflectance ratio. The arch shape is reproduced by the simulations, which assume a smooth surface. However, surface roughness on the scale of the particles, such as the Hapke and van Horn (Hapke, B., van Horn, H. [1963]. J. Geophys. Res. 68, 4545–4570) fairy castles that can spontaneously form when sprinkling a fine powder, leads to monotonic reddening. A further consequence of this form of microscopic roughness (being indistinct without the use of a microscope) is a flattening of the disk function at visible wavelengths, i.e. Lommel–Seeliger-type scattering. The experiments further reveal monotonic reddening for reflectance ratios at near-IR wavelengths. The simulations fail to reproduce this particular reddening, and we suspect that it results from roughness on the surface of the particles. Given that the regolith of atmosphereless Solar System bodies is composed of small particles, our results indicate that the prevalence of monotonic reddening and Lommel–Seeliger-type scattering for these bodies results from microscopic roughness, both in the form of structures built by the particles and roughness on the surface of the particles themselves. It follows from the singular Viking 1 observation that the surface in front of the lander was composed of semi-transparent particles, and was smooth on the scale of the particle size.

Early brain injury linearly correlates with reduction in cerebral perfusion pressure during the hyperacute phase of subarachnoid hemorrhage

BACKGROUND It is unclear how complex pathophysiological mechanisms that result in early brain injury (EBI) after subarachnoid hemorrhage (SAH) are triggered. We investigate how peak intracranial pressure (ICP), amount of subarachnoid blood, and hyperacute depletion of cerebral perfusion pressure (CPP) correlate to the onset of EBI following experimental SAH. METHODS An entire spectrum of various degrees of SAH severities measured as peak ICP was generated and controlled using the blood shunt SAH model in rabbits. Standard cardiovascular monitoring, ICP, CPP, and bilateral regional cerebral blood flow (rCBF) were continuously measured. Cells with DNA damage and neurodegeneration were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB). RESULTS rCBF was significantly correlated to reduction in CPP during the initial 15 min after SAH in a linear regression pattern (r (2) = 0.68, p < 0.001). FJB- and TUNEL-labeled cells were linearly correlated to reduction in CPP during the first 3 min of hemorrhage in the hippocampal regions (FJB: r (2) = 0.50, p < 0.01; TUNEL: r (2) = 0.35, p < 0.05), as well as in the basal cortex (TUNEL: r (2) = 0.58, p < 0.01). EBI occurred in animals with severe (relative CPP depletion >0.4) and moderate (relative CPP depletion >0.25 but <0.4) SAH. Neuronal cell death was equally detected in vulnerable and more resistant brain regions. CONCLUSIONS The degree of EBI in terms of neuronal cell degeneration in both the hippocampal regions and the basal cortex linearly correlates with reduced CPP during hyperacute SAH. Temporary CPP reduction, however, is not solely responsible for EBI but potentially triggers processes that eventually result in early brain damage.