A pilot study (NCT00316563) to determine if delta-9-tetrahydrocannabinol (THC) can improve taste and smell (chemosensory) perception as well as appetite, caloric intake, and quality of life (QOL) for ...cancer patients with chemosensory alterations.
Adult advanced cancer patients, with poor appetite and chemosensory alterations, were recruited from two sites and randomized in a double-blinded manner to receive either THC (2.5 mg, Marinol®; Solvay Pharma Inc., n = 24) or placebo oral capsules (n = 22) twice daily for 18 days. Twenty-one patients completed the trial. At baseline and posttreatment, patients completed a panel of patient-reported outcomes: Taste and Smell Survey, 3-day food record, appetite and macronutrient preference assessments, QOL questionnaire, and an interview.
THC and placebo groups were comparable at baseline. Compared with placebo, THC-treated patients reported improved (P = 0.026) and enhanced (P < 0.001) chemosensory perception and food ‘tasted better’ (P = 0.04). Premeal appetite (P = 0.05) and proportion of calories consumed as protein increased compared with placebo (P = 0.008). THC-treated patients reported increased quality of sleep (P = 0.025) and relaxation (P = 0.045). QOL scores and total caloric intake were improved in both THC and placebo groups.
THC may be useful in the palliation of chemosensory alterations and to improve food enjoyment for cancer patients.
Issues of Cancer Survivorship addresses the issues of experiencing life with cancer, from diagnosis to living with and beyond cancer. It focuses on the psychological impact of cancer, including ...psychological distress, the uncertainty, the short-term and long-term side effects of treatments, body image issues, spirituality/religious issues, impact of the disease on finances, impact on family relationships, and social support. In addition, the book covers cancer in children and secondary cancers as a result of the treatment they received, which is increasingly an issue as patients are living longer.
Abstract Nitric oxide (NO) is known to be a potent inhibitor of platelet activation and adhesion. Healthy endothelial cells that line the inner walls of all blood vessels exhibit a NO flux of ...0.5–4 × 10−10 mol cm−2 min−1 that helps prevent thrombosis. Materials with a NO flux that is equivalent to this level are expected to exhibit similar anti-thrombotic properties. In this study, five biomedical grade polymers doped with S- nitroso- N- acetylpenicillamine (SNAP) were investigated for their potential to control the release of NO from the SNAP within the polymers, and further control the release of SNAP itself. SNAP in the Elast-eon E2As polymer creates an inexpensive, homogeneous coating that can locally deliver NO (via thermal and photochemical reactions) as well slowly release SNAP. Furthermore, SNAP is surprisingly stable in the E2As polymer, retaining 82% of the initial SNAP after 2 months storage at 37 °C. The E2As polymer containing SNAP was coated on the walls of extracorporeal circulation (ECC) circuits and exposed to 4 h blood flow in a rabbit model of extracorporeal circulation to examine the effects on platelet count, platelet function, clot area, and fibrinogen adsorption. After 4 h, platelet count was preserved at 100 ± 7% of baseline for the SNAP/E2As coated loops, compared to 60 ± 6% for E2As control circuits ( n = 4). The SNAP/E2As coating also reduced the thrombus area when compared to the control (2.3 ± 0.6 and 3.4 ± 1.1 pixels/cm2 , respectively). The results suggest that the new SNAP/E2As coating has potential to improve the thromboresistance of intravascular catheters, grafts, and other blood-contacting medical devices, and exhibits excellent storage stability compared to previously reported NO release polymeric materials.
NO release from optimized patches is able to significantly reduce the A. baumannii infection after 24h application to scald burn wounds. Display omitted
Nitric oxide (NO) has many biological roles ...(e.g. antimicrobial agent, promoter of angiogenesis, prevention of platelet activation) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2±0.7wt.%) and Tecophilic SP-60D-20 (22.5±1.1wt.%)) were doped with 25wt.% DBHD/N2O2 and 10wt.% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with the lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rate of the PLGA additive, thereby providing a more acidic environment that increases the rate of NO release from the NO donor. The optimal NO releasing and control SG-80A patches were then applied to scald burn wounds that were infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24h (∼4 log reduction). The NO release patches are also able to reduce the level of transforming growth factor-β in comparison to controls, which can enhance re-epithelialization, decrease scarring and reduce migration of bacteria. The combined DBHD/N2O2 and PLGA-doped polymer patches, which could be replaced periodically throughout the wound healing process, demonstrate the potential to reduce risk of bacterial infection and promote the overall wound healing process.
This article uses a formal systematic review to examine the extent to which literature discussing collaborative approaches to water governance reflects understanding and awareness of power-related ...considerations. It makes the case that an analytical approach grounded in theory on power can facilitate assessment of the factors affecting collaboration by identifying the multiscalar, interrelated mechanisms through which power affects collaborative processes and outcomes. Through the review process, it became apparent that fully accounting for power will better enable scholars to link together seemingly disparate conditions for collaborative success (e.g., inclusion, decision-making power, capacity). A power-based approach also incorporates broad socioeconomic factors that fundamentally shape processes but often lie outside the analytical scope of local or regional studies on collaboration. Accounting for power, in the forms and scales identified, will result in better -designed, more effective collaborative approaches to water governance.
The prolonged and localized delivery of nitric oxide (NO), a potent antithrombotic and antimicrobial agent, has many potential biomedical applications. In this work, the origin of the long-term ...storage stability and sustained NO release mechanism of S-nitroso-N-acetyl-d-penicillamine (SNAP)-doped CarboSil 20 80A polymer, a biomedical thermoplastic silicone-polycarbonate-urethane, is explored. Long-term (22 days) localized NO release is achieved by utilizing a cross-linked silicone rubber as topcoats, which can greatly reduce the amount of SNAP, NAP, and NAP disulfide leaching from the SNAP-doped CarboSil films, as measured by LC–MS. Raman spectroscopy and powder X-ray diffraction characterization of SNAP-doped CarboSil films demonstrate that a polymer–crystal composite is formed during the solvent evaporation process when SNAP exceeds its solubility in CarboSil (ca. 3.4–4.0 wt %). Further, when exceeding this solubility threshold, SNAP exists in an orthorhombic crystal form within the bulk of the polymer. The proposed mechanism of sustained NO release in SNAP-doped CarboSil is that the solubilized SNAP in the polymer matrix decomposes and releases NO, primarily in the water-rich regions near the polymer/solution interface, and the dissolved SNAP in the bulk polymeric phase becomes unsaturated, resulting in the dissolution of crystalline SNAP within the bulk of the polymer. This is a very slow process that ultimately leads to NO release at the physiological flux levels for >3 weeks. The increased stability of SNAP within CarboSil is attributed to the intermolecular hydrogen bonds between the SNAP molecules that crystallize. This crystallization also plays a key role in maintaining RSNO stability within the CarboSil polymer for >8 months at 37 °C (88.5% remains). Further, intravascular catheters fabricated with this new material are demonstrated to significantly decrease the formation of Staphylococcus aureus biofilm (a leading cause of nosocomial bloodstream infections) (in vitro) over a 7 day period, with 5 log units reduction of viable cell count on catheter surfaces. It is also shown that the NO release catheters can greatly reduce thrombus formation on the catheter surfaces during 7 h implantation in rabbit veins, when compared to the control catheters fabricated without SNAP. These results suggest that the SNAP-doped CarboSil system is a very attractive new composite material for creating long-term NO release medical devices with increased stability and biocompatibility.
Implantable medical devices are an integral part of primary/critical care. However, these devices carry a high risk for blood clots, caused by platelet aggregation on a foreign body surface. This ...study focuses on the development of a simplified approach to create nitric oxide (NO) releasing intravascular electrochemical oxygen (O2) sensors with increased biocompatibility and analytical accuracy. The implantable sensors are prepared by embedding S-nitroso-N-acetylpenacillamine (SNAP) as the NO donor molecule in the walls of the catheter type sensors. The SNAP-impregnated catheters were prepared by swelling silicone rubber tubing in a tetrahydrofuran solution containing SNAP. Control and SNAP-impregnated catheters were used to fabricate the Clark-style amperometric PO2 sensors. The SNAP-impregnated sensors release NO under physiological conditions for 18 d as measured by chemiluminescence. The analytical response of the SNAP-impregnated sensors was evaluated in vitro and in vivo. Rabbit and swine models (with sensors placed in both veins and arteries) were used to evaluate the effects on thrombus formation and analytical in vivo PO2 sensing performance. The SNAP-impregnated PO2 sensors were found to more accurately measure PO2 levels in blood continuously (over 7 and 20 h animal experiments) with significantly reduced thrombus formation (as compared to controls) on their surfaces.
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•Simplified method to prepare nitric oxide (NO) releasing IV electrochemical PO2 sensors.•S-nitroso-N-acetyl-penicillamine impregnation of PO2 catheter walls releases the NO.•NO release results in less thrombosis on the outer surface of PO2 sensors placed in vivo.•Less thrombus yields improved accuracy in real time monitoring of PO2 levels in vivo.
Silicone rubber (SR) tubing is soaked in a swelling solution to impregnate the entire tubing wall with S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-silicone rubber tubing is used to fabricate ...extracorporeal circulation (ECC) loops that delivers nitric oxide (NO), a potent inhibitor of platelet adhesion/activation, and can significantly reduce thrombosis in a rabbit model of thrombogenicity. Display omitted
Blood-contacting devices, including extracorporeal circulation (ECC) circuits, can suffer from complications due to platelet activation and thrombus formation. Development of nitric oxide (NO) releasing polymers is one method to improve hemocompatibility, taking advantage of the ability of low levels of NO to prevent platelet activation/adhesion. In this study a novel solvent swelling method is used to load the walls of silicone rubber tubing with the NO donor S-nitroso-N-acetylpenicillamine (SNAP). This SNAP-silicone rubber tubing exhibits an NO flux of ca. 1×10−10molcm−2min−1, which mimics the range of NO release from the normal endothelium, which is stable for at least 4h. Images of the tubing before and after swelling, obtained via scanning electron microscopy, demonstrate that this swelling method has little effect on the surface properties of the tubing. The SNAP-loaded silicone rubber and silicone rubber control tubing are used to fabricate ECC circuits that are evaluated in a rabbit model of thrombogenicity. After 4h of blood flow, the SNAP-loaded silicone rubber circuits were able to preserve the blood platelet count at 64% of baseline (vs. 12% for silicone rubber control). A 67% reduction in the degree of thrombus formation within the thrombogenicity chamber was also observed. This study demonstrates the ability to improve the hemocompatibility of existing/commercial silicone rubber tubing via a simple solvent swelling-impregnation technique, which may also be applicable to other silicone-based blood-contacting devices.
Localized nitric oxide (NO) release can be achieved from biomedical grade polymers doped with S-nitroso-N-acetylpenicillamine (SNAP). Despite the promising in vitro and in vivo biocompatibility results reported for these NO releasing polymers, many of these materials may face challenges in being translated to clinical applications, especially in the areas of polymer processing and manufacturing. In this study, we report a solvent swelling-impregnation technique to incorporate SNAP into extracorporeal circuit (ECC) tubing. These NO-releasing ECCs were able to attenuate the activation of platelets and maintain their functionality, while significantly reducing the extent of thrombus formation during 4h blood flow in the rabbit model of thrombogenicity.
Abstract Nitric oxide (NO) releasing (NORel) materials have been extensively investigated to create localized increases in NO concentration by the proton driven diazeniumdiolate-containing polymer ...coatings and demonstrated to improve extracorporeal circulation (ECC) hemocompatibility. In this work, the NORel polymeric coating composed of a diazeniumdiolated dibutylhexanediamine (DBHD-N2 O2 )-containing hydrophobic Elast-eon™ (E2As) polyurethane was combined with a direct thrombin inhibitor, argatroban (AG), and evaluated in a 4 h rabbit thrombogenicity model without systemic anticoagulation. In addition, the immobilizing of argatroban to E2As polymer was achieved by either a polyethylene glycol-containing (PEGDI) or hexane methylene (HMDI) diisocyanate linker. The combined polymer film was coated on the inner walls of ECC circuits to yield significantly reduced ECC thrombus formation compared to argatroban alone ECC control after 4 h blood exposure (0.6 ± 0.1 AG/HMDI/NORel vs 1.7 ± 0.2 cm2 AG/HMDI control). Platelet count (2.8 ± 0.3 AG/HMDI/NORel vs 1.9 ± 0.1 × 108 /ml AG/HMDI control) and plasma fibrinogen levels were preserved after 4 h blood exposure with both the NORel/argatroban combination and the AG/HMDI control group compared to baseline. Platelet function as measured by aggregometry remained near normal in both the AG/HMDI/NORel (63 ± 5%) and AG/HMDI control (58 ± 7%) groups after 3 h compared to baseline (77 ± 1%). Platelet P-selectin mean fluorescence intensity (MFI) as measured by flow cytometry also remained near baseline levels after 4 h on ECC to ex vivo collagen stimulation (16 ± 3 AG/HMDI/NORel vs 11 ± 2 MFI baseline). These results suggest that the combined AG/HMDI/NORel polymer coating preserves platelets in blood exposure to ECCs to a better degree than AG/PEGDI/NORel, NORel alone or AG alone. These combined antithrombin, NO-mediated antiplatelet effects were shown to improve thromboresistance of the AG/HMDI/NORel polymer-coated ECCs and move potential nonthrombogenic polymers closer to mimicking vascular endothelium.
Contentious water problems are increasingly being addressed using collaborative approaches to governance. Despite trends toward more inclusive governance, governments continue to play important roles ...in the initiation of collaboration, provision of institutional and financial support, and approval and implementation of policies and decisions. This study used power theory to structure an analysis of the actions and motivations of the state at various stages in the policy making and decision making cycle. Research assessed the potential of collaboration to generate better social and environmental outcomes. Empirical cases in Ontario and Alberta, Canada, both characterized by the participation of powerful natural resource industries, were used to generate insights. Results reveal that the provincial governments exerted power from agenda setting through to implementation in response to socioeconomic, political and cultural stimuli at multiple scales in ways that reproduced existing power structures. The position and activities of the state, in these cases, challenged the potential of collaboration to achieve desired social and environmental outcomes.
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