Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke

<p>Abstract</p> <p>Background</p> <p>Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting.</p> <p>Results</p> <p>Here, we demonstrate that minocycline attenuates both <it>in vitro </it>(oxygen glucose deprivation) and <it>in vivo </it>(middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury.</p> <p>Conclusion</p> <p>The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.</p

Mutations in Putative Mutator Genes of Mycobacterium tuberculosis Strains of the W-Beijing Family

Alterations in genes involved in the repair of DNA mutations (mut genes) result in an increased mutation frequency and better adaptability of the bacterium to stressful conditions. W-Beijing genotype strains displayed unique missense alterations in three putative mut genes, including two of the mutT type (Rv3908 and mutT2) and ogt. These polymorphisms were found to be characteristic and unique to W-Beijing phylogenetic lineage. Analysis of the mut genes in 55 representative W-Beijing isolates suggests a sequential acquisition of the mutations, elucidating a plausible pathway of the molecular evolution of this clonal family. The acquisition of mut genes may explain in part the ability of the isolates of W-Beijing type to rapidly adapt to their environment

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Volumetric Analysis of Gallbladder in Extremely Premature Infants

Background: We hypothesized that gallbladder (GB) volume is affected by serial changes during the early infancy period in extremely premature infants. Methods: We conducted a prospective study of extremely premature infants admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Fukushima City, Japan between January 2014 and December 2015. GB volume was measured by an abdominal ultrasound ellipsoid method between Day 0 and Day 56 after birth within 60 minutes before enteral feeding. We calculated GB volume (mL)/weight (kg), which was evaluated as GV/W. Results: In total, 30 infants were included. The median gestational age of the infants was 26 weeks 5 days (range, 23 weeks 1 day–28 weeks 6 days), and the median birth weight was 731 g (range, 398–1220 g). The detection rate of GB decreased in the infants over time; the rates were > 93% between Day 0 and Day 7 and < 77% between Day 10 and Day 56 after birth. GV/W decreased in the infants over time. The median GV/W values were 0.18 (range, 0.05–0.59) in infants on admission and constantly < 0.05 in those between Day 10 and Day 56 after birth. There was no correlation of GV/W with clinical variables after birth. Conclusion: It is considered that GB volume is not affected by serial changes without nonfavorable course of enteral nutrition