Non-equivalence of antibiotic generic drugs and risk for intensive care patients

Background: The underlying axiom in applying generic drugs is the equivalence of their active ingredient with the (usually more expensive) innovator product, an all-embracing statement with the insidious result that physicians assume that the generic products have been subjected to the same rigorous testing regimens as the brand-name products. The present paper presents novel experimental data on an investigator-blinded comparison between the innovator imipenem antibiotic, and a number of its generics. Methods: Particulate matter contamination of each group was visualized by means of a membrane filter method. Functional studies in an animal model–the dorsal skinfold chamber technique in mice-designed to simulate the state of microcirculatory dysfunction in intensive care patients was performed, in order to assess the influence of the particulate matter of each group on the functional capillary density of the striated skin muscle, after their intravenous injection. Results: The results showed massive particulate contamination of the generics, in a size range relevant for impacting the microcirculation. The particulate contamination contributed in some generic groups to a significant shutdown of tissue perfusion. Conclusion: The presented data underscore the need to raise the regulatory barriers for the entry of generics to the market, well beyond the simplistic proof of “bioequivalence”, which in no measure deals with the essential questions of quality and patient safety. If generics are used, they should be tested by a filter technique and optical microscopy, to ensure the absence especially of small particulate contaminants and their purity

Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation

Background: Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods: One gram each of either a porous beta-tricalcium phosphate (β-TCP) or an hydroxyapatite/silicon dioxide (HA/SiO2)-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results: Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions: This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting

Gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441.

International audienceBackground: During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles (AuNPs), which differed in size and purification grade (presence or absence of sodium citrate residues on the particle surface) in vitro, in the human alveolar type-II (ATII)-like cell lines A549 and NCIH441

NEOWISE-R Observation of the Coolest Known Brown Dwarf

The Wide-field Infrared Survey Explorer (WISE) spacecraft has been reactivated as NEOWISE-R to characterize and search for Near Earth Objects. The brown dwarf WISE J085510.83-071442.5 has now been reobserved by NEOWISE-R, and we confirm the results of Luhman (2014b), who found a very low effective temperature ($\approx 250$ K), a very high proper motion (8.1 +/- 0.1 arcsec/yr) , and a large parallax (454 +/- 45 mas). The large proper motion has separated the brown dwarf from the background sources that influenced the 2010 WISE data, allowing a measurement of a very red WISE color of W1-W2 $> 3.9$ mag. A re-analysis of the 2010 WISE astrometry using only the W2 band, combined with the new NEOWISE-R 2014 position, gives an improved parallax of 448 +/- 33 mas and proper motion of 8.08 +/- 0.05\; arcsec/yr. These are all consistent with Luhman (2014b).Comment: 6 pages, AJ accepte

Barrier functions and paracellular integrity in human cell culture models of the proximal respiratory unit.

International audienceAirway epithelial cells provide a barrier to the translocation of inhaled materials. Tight (TJ) and adherens junctions (AJ) play a key role in maintaining barrier functions, and are responsible for the selective transport of various substances through the paracellular pathway. In this study we compared a bronchial cell line (16HBE14o-) and primary bronchial cells (HBEC), both cocultivated with the fibroblast cell line Wi-38, with respect to their structural differentiation and their reaction to cytokine stimulation. HBEC formed a pseudostratified epithelial layer and expressed TJ and AJ proteins after 2 weeks in coculture. Mucus-producing and ciliated cells were found within 24 days. Additionally, a beating activity of the ciliated HBEC (14-19 Hz) could be detected. 16HBE14o-in coculture showed a multilayered growth without differentiation to a pseudostratified airway epithelium. Simultaneous exposure to TNF-a-and IFN-c-induced significant changes in barrier function and paracellular permeability in the cocultures of HBEC/Wi-38 but not in the 16HBE14o-/Wi-38. In summary, HBEC in coculture mimic the structure of native polarized bronchial epithelium showing basal, mucus-producing and ciliated cells. Our system provides an opportunity to examine the factors that influence barrier and mucociliary function of bronchial epithelium within a time frame of 3 weeks up to 3 months in an in vivo-like differentiated model

Acute Morphological and Toxicological Effects in a Human Bronchial Coculture Model after Sulfur Mustard Exposure.

International audienceSulfur mustard (SM) is a strong alkylating agent. Inhalation of SM causes acute lung injury accompanied by severe disruption of the airway barrier. In our study, we tested the acute effects after mustard exposure in an in vitro coculture bronchial model of the proximal barrier. To achieve this, we seeded normal human bronchial epithelial explant-outgrowth cells (HBEC) together with lung fibroblasts as a bilayer on filter plates and exposed the bronchial model after 31 days of differentiation to various concentrations of SM (30, 100, 300, and 500mM). The HBEC formed confluent layers, expressing functional tight junctions as measured by transepithelial electrical resistance (TER). Mucus production and cilia formation reappeared in the coculture model. TER was measured after 2 and 24 h following treatment. Depending on the different concentrations , TER decreased in the first 2 h up to 55% of the control at the highest concentration. After 24 h, TER seemed to recover because at concentrations up to 300mM values were equal to the control. SM induced a widening of intercellular spaces and a loss in cell-matrix adhesion. Mucus production increased with the result that cilia ceased to beat. Changes in the proinflammatory cytokines in-terleukin (IL)-6 and IL-8 were also observed. Apoptotic markers such as cytochrome c, p53, Fas-associated protein with death domain, and procaspase-3 were significantly induced at concentrations of less than 100mM. In summary, SM induces morphological and biochemical changes that reflect pathological effects of SM injury in vivo. It is hoped to use this coculture model to understand further the pathogenesis of SM-induced barrier injury and to search for novel approaches in SM therapy

Discovery of a Bright Field Methane (T-type) Brown Dwarf by 2MASS

We report the discovery of a bright (J = 13.83$\pm$0.03) methane brown dwarf, or T dwarf, by the Two Micron All Sky Survey. This object, 2MASSI J0559191-140448, is the first brown dwarf identified by the newly commissioned CorMASS instrument mounted on the Palomar 60-inch Telescope. Near-infrared spectra from 0.9 - 2.35 \micron show characteristic CH$_4$ bands at 1.1, 1.3, 1.6, and 2.2 \micron, which are significantly shallower than those seen in other T dwarfs discovered to date. Coupled with the detection of an FeH band at 0.9896 \micron and two sets of K I doublets at J-band, we propose that 2MASS J0559-14 is a warm T dwarf, close to the transition between L and T spectral classes. The brightness of this object makes it a good candidate for detailed investigation over a broad wavelength regime and at higher resolution.Comment: 21 pages, 3 figures, 2 tables, accepted to AJ for publication August 200

Discovery of a Brown Dwarf Companion to Gliese 570ABC: A 2MASS T Dwarf Significantly Cooler than Gliese 229B

We report the discovery of a widely separated (258\farcs3\pm0\farcs4) T dwarf companion to the Gl 570ABC system. This new component, Gl 570D, was initially identified from the Two Micron All Sky Survey (2MASS). Its near-infrared spectrum shows the 1.6 and 2.2 \micron CH$_4$ absorption bands characteristic of T dwarfs, while its common proper motion with the Gl 570ABC system confirms companionship. Gl 570D (M$_J$ = 16.47$\pm$0.07) is nearly a full magnitude dimmer than the only other known T dwarf companion, Gl 229B, and estimates of L = (2.8$\pm$0.3)x10$^{-6}$ L_{\sun} and T$_{eff}$ = 750$\pm$50 K make it significantly cooler and less luminous than any other known brown dwarf companion. Using evolutionary models by Burrows et al. and an adopted age of 2-10 Gyr, we derive a mass estimate of 50$\pm$20 M$_{Jup}$ for this object.Comment: 13 pages, 2 figures, 2 tables, accepted by ApJ

Discovery of Four Field Methane (T-type) Dwarfs with the Two Micron All-Sky Survey

We report the discovery of four field methane ( T -type) brown dwarfs using Two Micron All-Sky Survey (2MASS) data. One additional methane dwarf, previously discovered by the Sloan Digital Sky Survey, was also identified. Near-infrared spectra clearly show the 1.6 and 2.2 m CH4 absorption bands characteristic of objects with Teff 1300 K as well as broadened H2O bands at 1.4 and 1.9 m. Comparing the spectra of these objects with that of Gl 229B, we propose that all new 2MASS T dwarfs are warmer than 950 K, in order from warmest to coolest: 2MASS J1217-03, 2MASS J1225-27, 2MASS J1047+21, and 2MASS J1237+65. Based on this preliminary sample, we find a warm T dwarf surface density of 0.0022 T dwarfs deg-2, or 90 warm T dwarfs over the whole sky detectable to J \u3c 16. The resulting space density upper limit, 0.01 T dwarfs pc-3, is comparable to that of the first L dwarf sample from Kirkpatrick et al

Y Dwarf Trigonometric Parallaxes from the Spitzer Space Telescope

Y dwarfs provide a unique opportunity to study free-floating objects with masses <30 M_(Jup) and atmospheric temperatures approaching those of known Jupiter-like exoplanets. Obtaining distances to these objects is an essential step toward characterizing their absolute physical properties. Using Spitzer's Infrared Array Camera (IRAC) [4.5] images taken over baselines of ~2–7 years, we measure astrometric distances for 22 late-T and early Y dwarfs, including updated parallaxes for 18 objects and new parallax measurements for 4 objects. These parallaxes will make it possible to explore the physical parameter space occupied by the coldest brown dwarfs. We also present the discovery of six new late-T dwarfs, updated spectra of two T dwarfs, and the reclassification of a new Y dwarf, WISE J033605.04−014351.0, based on Keck/NIRSPEC J-band spectroscopy. Assuming that effective temperatures are inversely proportional to absolute magnitude, we examine trends in the evolution of the spectral energy distributions of brown dwarfs with decreasing effective temperature. Surprisingly, the Y dwarf class encompasses a large range in absolute magnitude in the near- to mid-infrared photometric bandpasses, demonstrating a larger range of effective temperatures than previously assumed. This sample will be ideal for obtaining mid-infrared spectra with the James Webb Space Telescope because their known distances will make it easier to measure absolute physical properties