Design of transdermal patch of ketoprofen by full factorial design for treatment of rheumatoid arthritis

Oral therapy of NSAIDs for treatment of rheumatoid arthritis causes gastric irritation and ulceration. In the present study transdermal patch of ketoprofen was developed using hydroxyl propyl methyl cellulose E5 and Eudragit S100. Patches were prepared by solvent evaporation method. Optimization was carried out by 32 factorial design with polymer concentration (HPMC E5) and plasticizer concentration (propylene glycol) as independent variables. Patches were evaluated for folding endurance, surface pH, drug content, percent moisture content, water uptake and swelling studies. Ex vivo permeation studies of optimized patch was performed using Franz diffusion cell while bioadhesion force and tensile strength were measured by using texture analyzer. Hydrophilic nature, swelling ability and wettability of polymer and plasticizer were responsible for increase in flux and bioadhesion with increase in their concentrations in the factorial batches. Swelling index of all formulations was in the range of 17.3 ±1.2 to 65.29 ±4.78 up to 3h. Flux obtained from all batches was in the range of 3.37±0.23 to 5.43±0.13µg/h/cm2. Anti-inflammatory studies using carrageenan-induced rat paw edema showed greater paw swelling reduction in case of ketoprofen patch. Cumulative percent drug permeation of optimized patch through nylon 66, Wistar rat skin and cadaver skin was found to be 92.3% >86.28 %>63.42% in 8h, while flux order was 6.073> 5.442 > 2.219 µg/h/cm2 respectively. The study concludes that transdermal patch of ketoprofen will be more efficacious with absence of gastric irritation observed in oral formulations. Keywords: Ketoprofen, Bioadhesion, HPMC E5, Flux, Backing membran

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

A high-velocity black hole on a Galactic-halo orbit in the solar neighborhood

Only a few of the dozen or so stellar-mass black holes have been observed away from the plane of the Galaxy$^1$. Those few could have been ejected from the plane as a result of a ``kick'' received during a supernova explosion, or they could be remnants of the population of massive stars formed in the early stages of evolution of the Galaxy. Determining their orbital motion should help to distinguish between these options. Here we report the transverse motion (in the plane of the sky) for the black hole X-ray nova XTE J1118+480 (refs 2-5), from which we derive a large space velocity. This X-ray binary has an eccentric orbit around the Galactic Centre, like most objects in the halo of the Galaxy, such as ancient stars and globular clusters. The properties of the system suggest that its age is comparable to or greater than the age of the Galactic disk. Only an extraordinary ``kick'' from a supernova could have launched the black hole into an orbit like this from a birth place in the disk of the Galaxy.Comment: 8 pages including 2 color figures. Additional figures and animation in http://www.iafe.uba.ar/astronomia/FM/mirabel.htm

A hot and fast ultra-stripped supernova that likely formed a compact neutron star binary.

Compact neutron star binary systems are produced from binary massive stars through stellar evolution involving up to two supernova explosions. The final stages in the formation of these systems have not been directly observed. We report the discovery of iPTF 14gqr (SN 2014ft), a type Ic supernova with a fast-evolving light curve indicating an extremely low ejecta mass (≈0.2 solar masses) and low kinetic energy (≈2 × 1050 ergs). Early photometry and spectroscopy reveal evidence of shock cooling of an extended helium-rich envelope, likely ejected in an intense pre-explosion mass-loss episode of the progenitor. Taken together, we interpret iPTF 14gqr as evidence for ultra-stripped supernovae that form neutron stars in compact binary systems

Vitamin D during pregnancy: why observational studies suggest deficiency and interventional studies show no improvement in clinical outcomes? A narrative review

International audienc

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

Accreting Black Holes

This chapter provides a general overview of the theory and observations of black holes in the Universe and on their interpretation. We briefly review the black hole classes, accretion disk models, spectral state classification, the AGN classification, and the leading techniques for measuring black hole spins. We also introduce quasi-periodic oscillations, the shadow of black holes, and the observations and the theoretical models of jets.Comment: 41 pages, 18 figures. To appear in "Tutorial Guide to X-ray and Gamma-ray Astronomy: Data Reduction and Analysis" (Ed. C. Bambi, Springer Singapore, 2020). v3: fixed some typos and updated some parts. arXiv admin note: substantial text overlap with arXiv:1711.1025

Foundations of Black Hole Accretion Disk Theory

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at http://www.livingreviews.org/lrr-2013-