Serum Penicillin G Levels Are Lower Than Expected in Adults within Two Weeks of Administration of 1.2 Million Units

When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3–4 weeks serum penicillin G levels are less than adequate (below MIC90 of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections

Purification of molybdenum oxide, growth and characterization of medium size zinc molybdate crystals for the LUMINEU program

The LUMINEU program aims at performing a pilot experiment on neutrinoless double beta decay of 100Mo using radiopure ZnMoO4 crystals operated as scintillating bolometers. Growth of high quality radiopure crystals is a complex task, since there are no commercially available molybdenum compounds with the required levels of purity and radioactive contamination. This paper discusses approaches to purify molybdenum and synthesize compound for high quality radiopure ZnMoO4 crystal growth. A combination of a double sublimation (with addition of zinc molybdate) with subsequent recrystallization in aqueous solutions (using zinc molybdate as a collector) was used. Zinc molybdate crystals up to 1.5 kg were grown by the low-thermal-gradient Czochralski technique, their optical, luminescent, diamagnetic, thermal and bolometric properties were tested.Comment: Contribution to Proc. of Int. Workshop on Radiopure Scintillators RPSCINT 2013, 17-20 September 2013, Kyiv, Ukraine; to be published in EPJ Web of Conferences; expected to be online in January 2014; 6 pages, 6 figures, and 3 table

Germ Line Origin and Somatic Mutations Determine the Target Tissues in Systemic AL-Amyloidosis

BACKGROUND: Amyloid is insoluble aggregated proteins deposited in the extra cellular space. About 25 different proteins are known to form amyloid in vivo and are associated with severe diseases such as Alzheimer's disease, prion diseases and type-2 diabetes. Light chain (AL) -amyloidosis is unique among amyloid diseases in that the fibril protein, a monoclonal immunoglobulin light chain, varies between individuals and that no two AL-proteins with identical primary structures have been described to date. The variability in tissue distribution of amyloid deposits is considerably larger in systemic AL-amyloidosis than in any other form of amyloidosis. The reason for this variation is believed to be based on the differences in properties of the amyloidogenic immunoglobulin light chain. However, there is presently no known relationship between the structure of an AL-protein and tissue distribution. METHODOLOGY/PRINCIPAL FINDINGS: We compared the pattern of amyloid deposition in four individuals with amyloid protein derived from variable light chain gene O18-O8, the source of a high proportion of amyloidogenic light chains, and in whom all or most of the fibril protein had been determined by amino acid sequencing. In spite of great similarities between the structures of the proteins, there was a pronounced variability in deposition pattern. We also compared the tissue distribution in these four individuals with that of four other patients with AL-amyloid derived from the L2-L16 gene. Although the interindividual variations were pronounced, liver and kidney involvement was much more evident in the latter four. CONCLUSIONS/SIGNIFICANCE: We conclude that although the use of a specific gene influences the tissue distribution of amyloid, each light chain exhibits one or more determinants of organ-specificity, which originate from somatic mutations and post-translational modifications. Eventual identification of such determinants could lead to improved treatment of patients with AL amyloidosis

Proteins That Promote Filopodia Stability, but Not Number, Lead to More Axonal-Dendritic Contacts

Dendritic filopodia are dynamic protrusions that are thought to play an active role in synaptogenesis and serve as precursors to spine synapses. However, this hypothesis is largely based on a temporal correlation between filopodia formation and synaptogenesis. We investigated the role of filopodia in synapse formation by contrasting the roles of molecules that affect filopodia elaboration and motility, versus those that impact synapse induction and maturation. We used a filopodia inducing motif that is found in GAP-43, as a molecular tool, and found this palmitoylated motif enhanced filopodia number and motility, but reduced the probability of forming a stable axon-dendrite contact. Conversely, expression of neuroligin-1 (NLG-1), a synapse inducing cell adhesion molecule, resulted in a decrease in filopodia motility, but an increase in the number of stable axonal contacts. Moreover, RNAi knockdown of NLG-1 reduced the number of presynaptic contacts formed. Postsynaptic scaffolding proteins such as Shank1b, a protein that induces the maturation of spine synapses, increased the rate at which filopodia transformed into spines by stabilization of the initial contact with axons. Taken together, these results suggest that increased filopodia stability and not density, may be the rate-limiting step for synapse formation

Taking the Heat out of the Burning-ice Debate: Potential and Future of Gas Hydrates

AbstractFinding gas hydrates to be a controversial, polarizing subject, the SBC Energy Institute (SBC-EI) developed a fact-based report, presenting: the key concepts; the status of exploration and production technologies; the status of research, development and demonstration (R,D&amp;D); and the environmental and safety challenges associated with the potential exploitation of this resource. In addition to leveraging the long involvement of Schlumberger in gas hydrates R,D&amp;D, the SBC-EI performed a literature review and engaged experts in the gas-hydrate field. The SBC-EI also analyzed patents from 50 offices worldwide, using the Thomson Derwent World Patents Index, and conducted a survey of gas-hydrate stakeholders to present the state of R,D&amp;D and a faithful picture of current thinking among academics and industry players involved in the field. Among various types of deposits, gas hydrates hosted in sand-dominated sediments both within permafrost and offshore stand out as the only resources that may be recovered in the near term. Contrary to common belief, these deposits can largely be identified using existing exploration technologies, with small adjustments. Stakeholders widely agree that depressurization is the best technology for producing gas hydrates from sand reservoirs, whereas interest in CO2-CH4-exchange production techniques have lost momentum. Nevertheless, gas-hydrate exploration and production raise significant technical challenges that, unresolved, could undermine the resource's commercial viability. R,D&amp;D remains a vital part of assessing the potential and economic viability of gas hydrates, and of addressing environmental and safety concerns. It is unlikely that gas hydrates will become competitive in gas-rich areas. But there is a much stronger possibility of commercial development in energy-deficient regions such as Asia, where gas-hydrate projects could alleviate energy-security concerns and strenghten energy independence. This would have revolutionary consequences for the energy sector. However, before this is possible, long-duration production tests are required. Japan is leading the way in this area and is aiming to achieve commercial operation by the end of the decade. This paper provides a fact-based review of existing knowledge on gas hydrates as a potential energy source. It is supported by two innovative analyses: (i) a comprehensive survey of gas-hydrate experts; and (ii) an in-depth examination of worldwide patents of gas-hydrate technologies.</jats:p

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