A Hemoglobin-Based Multifunctional Therapeutic: Polynitroxylated Pegylated Hemoglobin

Polynitroxylated pegylated hemoglobin (PNPH) as a multifunctional therapeutic takes advantage of the ability of hemoglobin (Hb) to transport oxygen, the antioxidative stress activities from the redox coupling of nitroxide and heme iron, and the hypercolloid properties of pegylation. The published preclinical data demonstrating that PNPH acts as a neurovascular protective multifunctional therapeutic in an animal model simulating prehospital resuscitation of traumatic brain injury (TBI) with hemorrhagic shock (HS) are reviewed. Preliminary results on the potential utility of PNPH for neurovascular protection in thrombolytic stroke therapy and for correction of vascular dysfunction through transfusion in sickle-cell disease (SCD) are also discussed. We hypothesize that with PNPH, Hb has more than been tamed--it has become a therapeutic and not just a nontoxic extracellular oxygen carrier--and that successful PNPH development as a multifunctional therapeutic that protects the neurovasculature and reduces oxidative stress may represent a paradigm shift in transfusion and critical care medicine, which may meet a number of unmet medical needs resulting from oxidative stress and inadequate blood flow, such as HS, TBI, SCD, and stroke

Planetary nebulae detected in the Spitzer Space Telescope GLIMPSE 3D Legacy Survey

Due to interstellar extinction, optical census of Galactic planetary nebulae (PNs) is highly incomplete, and some compact H ii regions might have been mis-classified as PNs. The problem is particularly severe in the Galactic plane where the extinction in the optical is significant and hampers the detections of PNs. Unlike optical observations, infrared (IR) observations are hardly affected by interstellar extinction, and provide a good opportunity to study highly obscured PNs. In this study, we use the data from the Spitzer Legacy Infrared Mid-Plane Survey Extraordinaire 3D (GLIMPSE 3D) to investigate the mid-infrared (MIR) properties of PNs and PN candidates. © 2012 International Astronomical Union.published_or_final_versionThe IAU Symposium No. 283: 'Planetary Nebulae: an Eye to the Future', Puerto de la Cruz, Tenerife, Spain, 25-29 July 2011. In International Astronomical Union Proceedings, 2011, v. 7 n. S283, p. 528-52

Maser Observations Of Westerlund 1 And Comprehensive Considerations On Maser Properties Of Red Supergiants Associated With Massive Clusters

published_or_final_versio

Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.

IntroductionPrevious studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury.MethodsNon-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40 μg/kg/dose), high-dose ALN (1,000 μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56 days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption.ResultsμCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14 days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56 days post-injury, and was able to partially preserve articular cartilage 14 days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56 days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14 days post-injury, with no change in bone formation at any time points.ConclusionsHigh-dose ALN treatment was able to prevent early trabecular bone loss and cartilage degeneration following non-invasive knee injury, but was not able to mitigate long-term joint degeneration. These data contribute to understanding the effect of bisphosphonates on the development of osteoarthritis, and may support the use of anti-resorptive drugs to prevent joint degeneration following injury, although further investigation is warranted

New modelling technique for aperiodic-sampling linear systems

A general input-output modelling technique for aperiodic-sampling linear systems has been developed. The procedure describes the dynamics of the system and includes the sequence of sampling periods among the variables to be handled. Some restrictive conditions on the sampling sequence are imposed in order to guarantee the validity of the model. The particularization to the periodic case represents an alternative to the classic methods of discretization of continuous systems without using the Z-transform. This kind of representation can be used largely for identification and control purposes.Comment: 19 pages, 0 figure

Identification of oxygen-rich late/post-asymptotic giant branch stars and water fountains via maser and infrared criteria

The transitional phase between the asymptotic giant branch (AGB) and post-AGB phases holds the key to our understanding of the late-stage metamorphosis of intermediate-mass stars. In particular, high velocity jets forming during this phase are suggested to contribute significantly to the shaping of planetary nebulae. For oxygen-rich stars, the rare "water fountains (WFs)" have been regarded as representative objects in this phase, and it is important to identify more of them for further studies. Here we briefly report the results of our latest OH and H2O maser surveys in which a new WF candidate (IRAS 19356+0754) was found. We also performed radiative transfer modelling on the spectral energy distributions (SEDs) of all known WFs. It is concluded that WFs might in fact not be the transitional objects, as opposed to previous belief. WFs could be AGB or post-AGB stars with no obvious similarities amongst their SEDs. Further efforts are still needed to improve the identification criteria.This work is supported by a grant awarded to JN from the Research Grants Council of Hong Kong (project code: HKU 703308P; HKU 704209P; HKU 704710P)

Do water fountain jets really indicate the onset of the morphological metamorphosis of circumstellar envelopes?

Small-scale bipolar jets with short dynamical ages from 'water-fountain' (WF) sources are regarded as an indication of the onset of circumstellar envelope morphological metamorphosis of intermediate-mass stars. Such a process usually happens at the end of the asymptotic giant branch (AGB) phase. However, recent studies found that WFs could be AGB stars or even early planetary nebulae. This fact prompted the idea that WFs may not necessarily be objects at the beginning of the morphological transition process. In the present work, we show that WFs could have different envelope morphologies by studying their spectral energy distribution profiles. SomeWFs have spherical envelopes that resemble usual AGB stars, while others have aspherical envelopes, which are more common to post-AGB stars. The results imply that WFs may not represent the earliest stage of morphological metamorphosis. We argue further that the dynamical age of a WF jet, which can be calculated from maser proper motions, may not be the real age of the jet. The dynamical age cannot be used to justify the moment when the envelope begins to become aspherical, nor to tell the concrete evolutionary status of the object. A WF jet could be the innermost part of a larger well-developed jet, which is not necessarily a young jet. © 2016 The Authors

Global sales of oral antibiotics formulated for children.

Objective: To investigate international consumption patterns of child-appropriate oral formulations of antibiotics by formulation type, with a focus on dispersible tablets, using data from a global sales database. Method: Antibiotic sales data for 2015 covering 74 countries and regional country groups were obtained from the MIDAS® pharmaceutical sales database, which includes samples of pharmacy wholesalers and retailers. The focus was on sales of child-appropriate oral formulations of Access antibiotics in the 2017 World Health Organization's WHO Model list of essential medicines for children. Sales volumes are expressed using a standard unit (i.e. one tablet, capsule, ampoule or vial or 5 mL of liquid). Sales were analysed by antibiotic, WHO region and antibiotic formulation. Findings: Globally, 17.7 billion standard units of child-appropriate oral antibiotic formulations were sold in 2015, representing 24% of total antibiotic sales of 74.4 billion units (both oral and parenteral) in the database. The top five child-appropriate Access antibiotics by sales volume were amoxicillin, amoxicillin with clavulanic acid, trimethoprim-sulfamethoxazole, cefalexin and ampicillin. The proportion of the top five sold for use as a syrup varied between 42% and 99%. Dispersible tablets represented only 22% of all child-appropriate oral formulation sales and made up only 15% of sales of 10 selected Access antibiotics on the model list for children. Conclusion: Globally most child-appropriate oral antibiotics were not sold as dispersible tablets in 2015, as recommended by WHO. There is a clear need for novel solid forms of antibiotics suitable for use in children