1,725,038 research outputs found
Tolerability of NGX-4010, a capsaicin 8% patch for peripheral neuropathic pain
No full textJohn F Peppin1, Kristine Majors2, Lynn R Webster3, David M Simpson4, Jeffrey K Tobias5, Geertrui F Vanhove51The Pain Treatment Center of the Bluegrass, Lexington, KY, USA; 2Integrated Clinical Trial Services, Inc, West Des Moines, IA, USA; 3Lifetree Clinical Research and Pain Clinic, Salt Lake City, UT, USA; 4Mount Sinai Medical Center, New York, NY, USA; 5NeurogesX, Inc, San Mateo, CA, USABackground/purpose: NGX-4010 (QUTENZA™; NeurogesX Inc, San Mateo, CA), a capsaicin 8% dermal patch, is licensed in the European Union for the treatment of peripheral neuropathic pain (PNP) in nondiabetic adults and in the United States for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN). While NGX-4010 treatment is associated with a low risk of systemic adverse events, patch application-related pain is common and may be managed with local cooling and/or oral analgesics. This article characterizes the tolerability of NGX-4010 and will help to guide any pain management.Methods: This integrated analysis of tolerability data collected from the NGX-4010 clinical study program included 1696 patients with PNP. Patch application-related pain on the treatment day was captured as Numeric Pain Rating Scale (NPRS) “pain now” scores while “average pain for the past 24 hours” NPRS scores were analyzed for 7 days following treatment. Other tolerability assessments included the percentage of patients completing ≥90% of the intended treatment duration and patients using medication for patch application-related pain.Results: The mean maximum change in “pain now” NPRS scores from pretreatment levels during and after patch application was 2.6 for all patients. This pain was transient and resolved following patch removal. Mean “average pain for the past 24 hours” NPRS scores returned to baseline by the evening of the treatment day for patients with PHN, and the evening of day 2 for patients with human immunodeficiency virus-associated distal sensory polyneuropathy or painful diabetic neuropathy. Repeated NGX-4010 applications did not affect the intensity of patch application-related pain. Almost all patients (≥98%) completed ≥90% of the full treatment duration, regardless of the number of treatments received.Conclusion: Transient patch application-related pain with NGX-4010 can be managed with local cooling and/or oral analgesics in nearly all cases. Patient adherence to the full intended treatment duration indicated that patch application-related pain was not a barrier to NGX-4010 use.Keywords: capsaicin 8% patch, NGX-4010, patch application-related pain, neuropathic pai
Mechanical and metallurgical properties of two-layered diamalloy 4010 and 2002 HVOF coating
No full textDiamalloy 4010, which is iron/molybdenum blend, is resistive to wear and Diamalloy 2002 is resistive to corrosion and wear. However, combination of these powders in layered structure, may offer advantages over the individual powders. In this case, mechanical properties of the resulting layered structure could be improved. Consequently, investigation into mechanical and metallurgical properties of the resulting structure is necessary. High Velocity Oxy-Fuel coating of Diamalloy 2002 [(WC12Co)50,Ni33Cr9Fe3.5Si2B2C0.5] powders and Diamalloy 4010 [Fe68Mo30Cr1.8Mn0.2] powders as well as two-layered coatings consisting of these powders was carried out. In the two-layered structure, Diamalloy 4010 was sprayed at the substrate surface while Diamalloy 2002 was sprayed on the top of Diamalloy 4010 coating. The coating microstructure and morphology were examined using optical microscope, Scanning Electron Microscope (SEM) and Energy Dispersive Spectroscopy (EDS). The indentation tests were carried out to evaluate the microhardness and surface elastic modulus of the resulting coatings. The mechanical properties of the coatings were examined through tensile and three-point bending tests. It was found that the coating produced for Diamalloy 2002 resulted in higher hardness than that corresponding to Diamalloy 4010. The failure mechanism of coating during tensile and three-point bending tests was mainly crack formation and propagation in the coating. The elastic modulus of coating produced from Diamalloy 2002 was higher than that of Diamalloy 4010 coating, which was due to the presence of 12% WC in the coating. The irregularities observed in the elastic limit of the curves indicated the formation of cracks in the coatings, which was particularly true for two layered coating. The shear stress developed at interface of the two-layered coating was responsible for the crack initiation in the coating. The deep cracks were also formed in the coatings after the tensile tests. This was attributed to the local stress centers, which increased the stress intensity under the tensile load
TOI-4010: A System of Three Large Short-Period Planets With a Massive Long-Period Companion
No full textWe report the confirmation of three exoplanets transiting TOI-4010
(TIC-352682207), a metal-rich K dwarf observed by TESS in Sectors 24, 25, 52,
and 58. We confirm these planets with HARPS-N radial velocity observations and
measure their masses with 8 - 12% precision. TOI-4010 b is a sub-Neptune ( days, , ) in the hot Neptune desert, and is one of the
few such planets with known companions. Meanwhile, TOI-4010 c ( days,
, ) and TOI-4010 d ( days, , )
are similarly-sized sub-Saturns on short-period orbits. Radial velocity
observations also reveal a super-Jupiter-mass companion called TOI-4010 e in a
long-period, eccentric orbit ( days and based on
available observations). TOI-4010 is one of the few systems with multiple
short-period sub-Saturns to be discovered so far.Comment: 26 pages, 16 figures, published in AJ; (v3) added missing citatio
Secretion of bacteriocins in Leuconostoc carnosum 4010
No full textBacteriocins are ribosomally synthesized antimicrobial proteins. They can be applied as biopreservatives in food processing for extending the shelf-life of food. Lactic acid bacterium Leuconostoc carnosum 4010 is Generally Recognized As Safe strain, which can be used as a protective culture in meat products. The strain 4010 produces three bacteriocins: leucocins A (LcnA), B (LebB) and C (LecC). For the secretion of bacteriocin out from the cell, bacteria usually use an ABC transporter, which is often dedicated to secrete only one bacteriocin. The leucocin operons in Ln. carnosum 4010 plasmids include genes for only one ABC transporter, namely LecXTS. The fact that Ln. carnosum 4010 produces three bacteriocins but only carries one bacteriocin transporter, raises a question, which leucocin(s) is/are translocated via LecXTS transporter. Therefore, the first aim of this study was to determine which bacteriocin(s) is/are secreted by LecXTS in Ln. carnosum 4010.
Ln. carnosum 4010 carries at least two plasmids. Leucocin A gene lcnA is located on the plasmid pLC4010-2, and leucocin B and C with transporter genes (lebB, lecC, lecXTS) are located on the plasmid pLC4010-1. In a previous work, two plasmid cured derivatives of Ln. carnosum 4010 have been made: the plasmid-free strain PCS-10, and the strain PCS-11 carrying only pLC4010-2. Neither of the derivatives secrete bacteriocins. In this study, the idea was to construct five recombinant plasmids containing the pLC4010-1 replication gene repB and a gene for erythromycin resistance ErmR. They were ligated with different sets of leucocin and transporter genes (repB-lebB-lecXTS-lecC-ErmR, repB-lebB-lecXTS-ErmR, repB-lebB-ErmR, repB-lecC-ErmR, and a vector control with only repB-ErmR). The constructs were aimed to be introduced into the two Ln. carnosum 4010 mutant strains PCS-10 and PCS-11. However, after several attempts of electroporation, no colonies were obtained. To acquire a testing plasmid for optimization of transformation, the ligation mixture for the smallest plasmid repB-ErmR was electroporated into another strain, Lactococcus lactis N8. The plasmid repB-ErmR was successfully obtained from Lc. lactis N8. For improving the efficiency of transformation, the plasmid repB-ErmR was isolated from Lc. lactis N8, and the plasmid was used in optimization of electroporation. The copy number of the plasmid was shown to be very low, as only a little amount of plasmid could be isolated from large culture volume. Even with optimized electroporation method, the repB-ErmR could not be electroporated into Ln. carnosum 4010. This indicates that the larger constructions are nearly impossible to be transferred into the strain Ln. carnosum 4010.
In conclusion, it was confirmed that the plasmid replication gene repB of Ln. carnosum 4010 is functional in Lc. lactis. Due to the low copy number of the plasmid repB-ErmR, the amount of plasmid was definitely a problem in electroporation. Therefore, for studying the efficiency of electroporation, the plasmid amount needs to be increased. Although the electroporation of repB-ErmR into Lc. lactis was successful, the results from Ln. carnosum electroporation after optimization indicate that the strain Ln. carnosum 4010 is difficult to be transformed
Union Pacific (UP) 4010
No full textA photograph postcard showing the Union Pacific (UP) 4010, 4-8-8-4, with westward extra, traveling down Echo Canyon near Devil's Slide, UT, 100 cars, 50 mph
St. Louis & San Francisco (SLSF) "Frisco" 4010
No full textA photograph print showing the St. Louis and San Francisco (SLSF) "Frisco" 4010, 2-8-2, St. Louis, MO
Union Pacific (UP) 3815 & 4010
No full textA photograph postcard showing the Union Pacific 3815, 4-6-6-4, and UP 4010, 4-8-8-4, on extra west, meeting extra east
(3) Faculty Commentary on Econ 4010
No full textBrian Brush of Marquette\u27s Department of Economics talks about Econ 4010
Tolerability of NGX-4010, a capsaicin 8% patch, in conjunction with three topical anesthetic formulations for the treatment of neuropathic pain
No full textLynn R Webster1, John F Peppin2, Frederick T Murphy3,4, Jeffrey K Tobias5, Geertrui F Vanhove51Lifetree Clinical Research and Pain Clinic, Lifetree Medical Inc, Salt Lake City, UT, USA; 2Clinical Research Division, The Pain Treatment Center of the Bluegrass, Lexington, KY, USA; 3Altoona Center for Clinical Research, Duncansville, PA, USA; 4University of Pennsylvania, School of Medicine, Philadelphia, PA, USA; 5NeurogesX Inc, San Mateo, CA, USABackground: The objective of this study was to assess the safety, tolerability, and preliminary efficacy of NGX-4010, a capsaicin 8% patch, following pretreatment with three different topical anesthetics in patients with peripheral neuropathic pain.Methods: This open-label, multicenter study enrolled 117 patients with post-herpetic neuralgia, HIV-associated distal sensory polyneuropathy, or painful diabetic neuropathy. Patients received pretreatment with one of three lidocaine 4%-based topical anesthetics (L.M.X.4® [Ferndale Laboratories Inc, Ferndale, MI], Topicaine® Gel [Estela Basso, Jupiter, FL], or Betacaine Enhanced Gel 4 [Tiberius Inc, Tampa, FL]) for 60 minutes followed by a single 60- or 90-minute NGX-4010 application, and were followed for 12 weeks. Tolerability and safety measures included “pain now” Numeric Pain Rating Scale (NPRS) scores, dermal assessments, medication use for treatment-related pain, adverse events (AEs), clinical laboratory parameters, physical examinations, and vital signs. The primary efficacy variable was the percentage change in mean NPRS scores for “average pain for the past 24 hours” from baseline to weeks 2 through 12.Results: Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated. Nearly all patients completed ≥90% of the planned NGX-4010 application duration. The most common treatment-related AEs, application-site burning and application-site pain, were transient, mostly mild or moderate, and could be adequately managed by local cooling or short-acting oral opioid analgesics. Although slightly more patients used medication for treatment-related discomfort following pretreatment with Topicaine compared with L.M.X.4 or Betacaine, there were no statistical differences between the topical anesthetics. Neuropathic pain reduction from baseline to weeks 2 through 12 was approximately 30% and was similar among the topical anesthetics; the proportion of responders ranged from 45% to 50%.Conclusion: Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated; no significant differences in the parameters measured were noted between the pretreatment groups.Keywords: neuropathic pain, capsaicin patch, tolerability, topical anesthetic
St. Louis & San Francisco (SLSF) "Frisco" 4010
No full textA photograph print showing the St. Louis and San Francisco (SLSF) "Frisco" 4010, 2-8-2, St. Louis, MO
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