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Jennifer Luk,1 Yong Lu,1 Amanda Ackermann,1 Xiaoxue Peng,1 Diane Bogdan,1 Michelino Puopolo,1 David E Komatsu,2 Simon Tong,3 Iwao Ojima,3,4 Mario J Rebecchi,1 Martin Kaczocha1,4 1Department of Anesthesiology, 2Department of Orthopedics, 3Department of Chemistry, 4Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY, USA Background: Metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG) yields arachidonic acid (AA), the precursor to proalgesic eicosanoids including prostaglandin E2 (PGE2). Diacylglycerol lipase β (DAGLβ) is an enzyme that synthesizes 2-AG and its inhibition reduces eicosanoid levels and produces antinociceptive effects in models of inflammatory pain. Here we test whether inhibition of DAGLβ produces antinociceptive effects in a model of postoperative pain.Methods: Rats were administered the selective DAGLβ inhibitor KT109 or vehicle and underwent plantar incision. Postsurgical pain/disability was examined using evoked (mechanical hyperalgesia), functional (incapacitance/weight bearing), and functional/spontaneous (locomotion) modalities.Results: Activity-based protein profiling confirmed that KT109 inhibited DAGLβ in the lumbar spinal cord (LSC) and brain, confirming that it is a systemically active DAGLβ inhibitor. Treatment with KT109 reduced basal 2-AG, AA, and PGE2 levels in the liver but not the brain, indicating that DAGLβ activity does not significantly contribute to basal PGE2 production within the central nervous system. Plantar incision elevated the levels of 2-AG and PGE2 in the LSC. Although KT109 did not alter postsurgical 2-AG levels in the LSC, it slightly reduced PGE2 levels. In contrast, the clinically efficacious cyclooxygenase inhibitor ketoprofen completely suppressed PGE2 levels in the LSC. Similarly, KT109 had no significant effect upon postsurgical 2-AG, AA, or PGE2 levels at the incision site, while ketoprofen abolished PGE2 production at this location. KT109 and ketoprofen reversed the weight bearing imbalance induced by plantar incision, yet neither KT109 nor ketoprofen had any significant effect on mechanical hyperalgesia. Treatment with ketoprofen partially but significantly rescued the locomotor deficit induced by incision while KT109 was without effect. Conclusion: DAGLβ is not the principal enzyme that controls 2-AG derived AA and PGE2 production after surgery, and inhibitors targeting this enzyme are unlikely to be efficacious analgesics superior to those already approved to treat acute postoperative pain. Keywords: pain, incision, surgery, endocannabinoid, 2-AG

Abstract In the present investigation, scratch resistance, chemical inertness, and corrosion resistance of methyl phenyl polysiloxane coatings on Fe 430 B structural steel with or without an organo-silane intermediate layer [...]

Luminal acidification provides the strongest physiological stimulus for duodenal HC[O.sup.-.sub.3] secretion. Various neurohumoral mechanisms are believed to play a role in acid-stimulated HC[O.sup.-.sub.3] secretion. Previous studies in the rat and human duodenum have shown that guanylin and Escherichia coli heat-stable toxin, both ligands of the transmembrane guanylyl cyclase receptor [guanylate cyclase C (GC-C)], are potent stimulators for duodenal HC[O.sup.-.sub.3] secretion. We postulated that the GC-C receptor plays an important role in acid-stimulated HC[O.sup.-.sub.3] secretion. In vivo perfusion studies performed in wild-type (WT) and GC-C knockout (KO) mice indicated that acid-stimulated duodenal HC[O.sup.-.sub.3] secretion was significantly decreased in the GC-C KO animals compared with the WT counterparts. Pretreatment with PD-98059, an MEK inhibitor, resulted in attenuation of duodenal HC[O.sup.-.sub.3] secretion in response to acid stimulation in the WT mice with no further effect in the KO mice. In vitro cGMP generation studies demonstrated a significant and comparable increase in cGMP levels on acid exposure in the duodenum of both WT and KO mice. In addition, a rapid, time-dependent phosphorylation of ERK was observed with acid exposure in the duodenum of WT mice, whereas a marked attenuation in ERK phosphorylation was observed in the KO animals despite equivalent levels of ERK in both groups of animals. On the basis of these studies, we conclude that transmembrane GC-C is a key mediator of acid-stimulated duodenal HC[O.sup.-.sub.3] secretion. Furthermore, ERK phosphorylation may be an important intracellular mediator of duodenal HC[O.sup.-.sub.3] secretion. acid-stimulated bicarbonate secretion; extracellular signal-related kinase phosphorylation; intracellular signaling

Flexible and semiflexible packagings can be manufactured by cast extrusion of plastic sheet and thermoforming of containers. Thermal stability is often required as packaging items after being thermoformed can come in contact with hot food/beverage, especially during hot filling operations. In this framework, the present study deals with the design and manufacturing by thermoforming of plastic containers that are, at the same time, compostable and suitable for high‐temperature applications (~100 °C). First, extrusion compounding of Poly(l‐lactic acid) (PLLA)‐based biodegradable polyester blends was performed. In particular, the effect on the material properties of different types of nucleating agents was investigated. Combinations of micro‐lamellar talc, poly(d‐lactic acid) (PDLA), ethylene bisstearamide (EBS), and titanium dioxide (TiO2) were studied. The formulations involving EBS boast the highest crystallinity and the fastest onset of the crystalline phase on sheets produced by cast extrusion. Conversely, the formulations involving TiO2 feature the lowest degree of crystallinity and the slowest onset of the crystalline phase. Combinations of talc and PDLA exhibit an intermediate behavior. Second, thermoforming of the plastic foils was performed. A very different trend of the crystallization after thermoforming is shown. Indeed, crystallinity is the highest for the formulations involving talc and PDLA, the lowest for the ones containing EBS. In conclusion, the biodegradable polyester blends are found to be suitable for the manufacturing of compostable and thermostable packaging items by cast extrusion and thermoforming. Final crystallization of the material and the resulting thermal stability can be fine‐tuned by modulating type and amount of nucleating agents. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48722. [ABSTRACT FROM AUTHOR]

Binary blends based on polylactic acid (PLA) and other biodegradable polyesters from renewable sources (namely, polybutylene succinate (PBS) and poly-3-hydroxybutyrate (PHB)) were prepared by reactive compounding extrusion. The achieved polymeric compounds were reprocessed by cast extrusion to manufacture the corresponding bioplastic sheets. Three different binary blends, one of which also including tocopherol, an oxygen scavenger, were investigated to ensure high-barrier of the bioplastic sheets to oxygen permeation. Physical, mechanical and chemical properties of the bioplastic sheets were, therefore, comparatively evaluated by differential scanning calorimetry, infrared spectroscopy, tensile tests and gas permeability. The experimental results showed a remarkable improvement in the oxygen barrier properties, especially on sheets manufactured in the PLA/PHB binary blend, without negatively affecting their thermo-mechanical response. Based on experimental evidences, the PLA/PHB binary blend is found to be extremely promising for the development of bio-based and biodegradable polymeric materials with low oxygen permeation, that is, for the development of suitable alternatives to conventional and highly pollutant oil-based plastics. [ABSTRACT FROM AUTHOR]

The present work is aimed at developing innovative solutions to enhance mechanical and physical properties of Poly(Lactic) Acid (PLA) blends, specifically designed for melt processing applications. Attention is drawn on dimensional accuracy and stability of PLA-based components manufactured by injection molding. PLA belongs to the class of bioplastic materials, entirely relying on renewable resources. It is a semi-crystalline linear aliphatic polyester, highly prone to recrystallize in harsh temperature conditions that can arise during transportation or storage of injection-molded components. Recrystallization is known to cause shrinkage of polymeric materials and, consequently, a marked warpage of components produced from them, causing scraps or parts that do not conform to the functional requirements. In this context, the experimental investigation deals with the effect of increasing amounts of micro-lamellar talc in PLA and Poly(butylene) Succinate Co-Adipate (PBSA) blends. In particular, the role of talc aliquot on dimensional accuracy and stability of injection-molded coffee capsules manufactured by PLA/PBSA blends is studied, with emphasis on the key role of recrystallization. For that purpose, commercial grade PLA and PBSA are compounded with micro-lamellar talc and several processing additives by a twin screw co-rotating extruder. The resulting compound is reprocessed to form coffee capsules by injection molding. Characterization tests include Differential Scanning Calorimetry (DSC), Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) spectroscopy and Field Emission Gun Scanning Electron Microscopy (FEG – SEM). Measurements of the characteristic dimensions of the molded components reveals the effect of increasing amounts of talc in PLA/PBSA blends on dimensional accuracy and stability properties of coffee capsules. Brewing tests allowed to identify the formulations that can ensure the utmost geometrical accuracy of the coffee capsules and their suitability for brewing in instant coffee machine. Based on experimental evidences, lowest shrinkage and improved stability are found on components manufactured by polymeric blends that involve the highest amount of talc. [ABSTRACT FROM AUTHOR]