Effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) on cerebrospinal fluid inflammation induced by endotoxin

Endotoxin triggers the subarachnoid inflammation of gram-negative meningitis. This study examined the ability of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) to block endotoxin-induced meningitis in rabbits. Intracisternal (ic) injection of 10-20 ng of meningococcal endotoxin induced high cerebrospinal fluid (CSF) concentrations of tumor necrosis factor (TNF) and CSF pleocytosis and increased CSF lactate concentrations. ic administration of rBPI23 significantly reduced meningococcal endotoxin-induced TNF release into CSF (P < .005), lactate concentrations (P < .001), and CSF white blood cell counts (P < .01). No such effect was observed in animals receiving intravenous rBPI23. Concentrations of rBPI23 in CSF were high after ic administration but low or undetectable after systemic administration. Thus, high concentrations of rBPI23 can effectively neutralize meningococcal endotoxin in CSF, but low CSF concentrations after systemic administration currently limit its potential usefulness as adjunctive drug treatment in gram-negative meningitis.

A rapid and efficient ion-exchange chromatography for Lu–Hf, Sm–Nd, and Rb–Sr geochronology and the routine isotope analysis of sub-ng amounts of Hf by MC-ICP-MS

The development and improvement of MC-ICP-MS instruments have fueled the growth of Lu–Hf geochronology over the last two decades, but some limitations remain. Here, we present improvements in chemical separation and mass spectrometry that allow accurate and precise measurements of 176Hf/177Hf and 176Lu/177Hf in high-Lu/Hf samples (e.g., garnet and apatite), as well as for samples containing sub-nanogram quantities of Hf. When such samples are spiked, correcting for the isobaric interference of 176Lu on 176Hf is not always possible if the separation of Lu and Hf is insufficient. To improve the purification of Hf, the high field strength elements (HFSE, including Hf) are first separated from the rare earth elements (REE, including Lu) on a first-stage cation column modified after Patchett and Tatsumoto (Contrib. Mineral. Petrol., 1980, 75, 263–267). Hafnium is further purified on an Ln-Spec column adapted from the procedures of Münker et al. (Geochem., Geophys., Geosyst., 2001, DOI: 10.1029/2001gc000183) and Wimpenny et al. (Anal. Chem., 2013, 85, 11258–11264) typically resulting in Lu/Hf < 0.0001, Zr/Hf < 1, and Ti/Hf < 0.1. In addition, Sm–Nd and Rb–Sr separations can easily be added to the described two-stage ion-exchange procedure for Lu–Hf. The isotopic compositions are measured on a Thermo Scientific Neptune Plus MC-ICP-MS equipped with three 1012 Ω resistors. Multiple 176Hf/177Hf measurements of international reference rocks yield a precision of 5–20 ppm for solutions containing 40 ppb of Hf, and 50–180 ppm for 1 ppb solutions (=0.5 ng sample Hf 0.5 in ml). The routine analysis of sub-ng amounts of Hf will facilitate Lu–Hf dating of low-concentration samples.