Characterization of highly stable liposomal and immunoliposomal formulations of vincristine and vinblastine

Liposome and immunoliposome formulations of two vinca alkaloids, vincristine and vinblastine, were prepared using intraliposomal triethylammonium sucroseoctasulfate and examined for their ability to stabilize the drug for targeted drug delivery in vivo. The pharmacokinetics of both the encapsulated drug (vincristine or vinblastine) and liposomal carrier were examined in Sprague Dawley rats, and the in vivo drug release rates determined. Anti-HER2 immunoliposomal vincristine was prepared from a human anti-HER2/neu scFv and studied for targeted cytotoxic activity in cell culture, and antitumor efficacy in vivo. Nanoliposome formulations of vincristine and vinblastine demonstrated similar pharmacokinetic profiles for the liposomal carrier, but increased clearance for liposome encapsulated vinblastine (t 1/2 = 9.7 h) relative to vincristine (t 1/2 = 18.5 h). Immunoliposome formulations of vincristine targeted to HER2 using an anti-HER2 scFv antibody fragment displayed a marked enhancement in cytotoxicity when compared to non-targeted liposomal vincristine control; 63- or 253-fold for BT474 and SKBR3 breast cancer cells, respectively. Target-specific activity was also demonstrated in HER2-overexpressing human tumor xenografts, where the HER2-targeted formulation was significantly more efficacious than either free vincristine or non-targeted liposomal vincristine. These results demonstrate that active targeting of solid tumors with liposomal formulations of vincristine is possible when the resulting immunoliposomes are sufficiently stabilized

Temperature, recreational fishing and diapause egg connections : dispersal of spiny water fleas (Bythotrephes longimanus)

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Biological Invasions 13 (2011): 2513-2531, doi:10.1007/s10530-011-0078-8.The spiny water flea (Bythotrephes longimanus) is spreading from Great Lakes coastal waters into northern inland lakes within a northern temperature-defined latitudinal band. Colonization of Great Lakes coastal embayments is assisted by winds and seiche surges, yet rapid inland expansion across the northern states comes through an overland process. The lack of invasions at Isle Royale National Park contrasts with rapid expansion on the nearby Keweenaw Peninsula. Both regions have comparable geology, lake density, and fauna, but differ in recreational fishing boat access, visitation, and containment measures. Tail spines protect Bythotrephes against young of the year, but not larger fish, yet the unusual thick-shelled diapausing eggs can pass through fish guts in viable condition. Sediment traps illustrate how fish spread diapausing eggs across lakes in fecal pellets. Trillions of diapausing eggs are produced per year in Lake Michigan and billions per year in Lake Michigamme, a large inland lake. Dispersal by recreational fishing is linked to use of baitfish, diapausing eggs defecated into live wells and bait buckets, and Bythothephes snagged on fishing line, anchor ropes, and minnow seines. Relatively simple measures, such as on-site rinsing of live wells, restricting transfer of certain baitfish species, or holding baitfish for 24 h (defecation period), should greatly reduce dispersal.Study of Lakes Superior and Michigan was funded from NSF OCE-9726680 and OCE-9712872 to W.C.K., OCE-9712889 to J. Churchill. Geographic survey sampling and Park studies in the national parks during 2008-2010 were funded by a grant from the National Park Service Natural Resource Preservation Program GLNF CESU Task Agreement No. J6067080012

Neglecting legumes has compromised human health and sustainable food production

The United Nations declared 2016 as the International Year of Pulses (grain legumes) under the banner 'nutritious seeds for a sustainable future'. A second green revolution is required to ensure food and nutritional security in the face of global climate change. Grain legumes provide an unparalleled solution to this problem because of their inherent capacity for symbiotic atmospheric nitrogen fixation, which provides economically sustainable advantages for farming. In addition, a legume-rich diet has health benefits for humans and livestock alike. However, grain legumes form only a minor part of most current human diets, and legume crops are greatly under-used. Food security and soil fertility could be significantly improved by greater grain legume usage and increased improvement of a range of grain legumes. The current lack of coordinated focus on grain legumes has compromised human health, nutritional security and sustainable food production.We thank World University Network (WUN) and research collaboration awards (UWA and the University of Leeds) for financial support. CHF thanks the Biotechnology and Biological Sciences Research Council (BBSRC UK (BB/M009130/1) and the European Union (KBBE-2012-6-311840; ECOSEED) for financial support. JWC thanks BBSRC (UK) and Wherry and Sons, (UK) for an industrial CASE studentship (BB/K501839/1). H-ML was supported by the Hong Kong RGC Collaborative Research Fund (CUHK3/CRF/11G), the Lo Kwee-Seong Biomedical Research Fund and Lee Hysan Foundation. Ka-Ming Fung, Qianwen Wang, Lydia Kit-Wah Siu, and Yihan Jiang of The Chinese University of Hong Kong assisted in the production of Fig. 2, Table 1 and the associated webpage, highlight and cover design. We thank Hari Upadhyaya for the images shown in Fig. 4. TAM and JMH thank the Western Australian Government, Department of Industry and Resources for financial support. The authors thank Bodhi‟s Bakery, Fremantle, Western Australia, for baking the bread and biscuits and Belmar Foods, Balcatta, Western Australia, for manufacturing and providing the pasta. BNK and HB are supported by Australian Research Council (ARC), ITRH – Legumes for Sustainable Agriculture (IH140100013). MJC and CHF thank the ARC (DP150103211) for financial support. AJM is supported by grant funding (BB/JJ004553/1 and BB/L010305/1) from the BBSRC and the John Innes Foundation.http://www.nature.com/nplantshb2017Plant Production and Soil Scienc

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Quantification of 18FDG in the Normal Colon-A First Step in Investigating Whether Its Presence Is a Marker of a Physiological Process.

The visibility of the colon in positron emission tomography (PET) scans of patients without gastrointestinal disease indicating the presence of 18F Fluorodeoxyglucose (18FDG) is well recognised, but unquantified and unexplained. In this paper a qualitative scoring system was applied to PET scans from 30 randomly selected patients without gastrointestinal disease to detect the presence of 18FDG in 4 different sections of the colon and then both the total pixel value and the pixel value per unit length of each section of the colon were determined to quantify the amount of 18FDG from a randomly selected subset of 10 of these patients. Analysis of the qualitative scores using a non-parametric ANOVA showed that all sections of the colon contained 18FDG but there were differences in the amount of 18FDG present between sections (p0.05), but a difference in the amount/unit length between sections (p<0.01) with only the caecum and ascending colon and the descending colon having a statistically significant difference (p<0.05). These results are consistent since the eye is drawn to focal localisation of the 18FDG when qualitatively scoring the scans. The presence of 18FDG in the colon is counterintuitive since it must be passing from the blood to the lumen through the colonic wall. There is no active mechanism to achieve this and therefore we hypothesise that the transport is a passive process driven by the concentration gradient of 18FDG across the colonic wall. This hypothesis is consistent with the results obtained from the qualitative and quantitative measures analysed

Factors controlling streambed coverage of Didymosphenia geminata in two regulated streams in the Colorado Front Range

Didymosphenia geminata is a stalk-forming freshwater diatom which was historically found primarily in oligotrophic lakes and streams, but has recently become a nuisance species in many lotic systems worldwide. In the last 5–8 years, D. geminata has become established in Boulder Creek and South Boulder Creek, two regulated montane streams in the Front Range of the Colorado Rocky Mountains. Factors that may influence the growth of D. geminata were monitored during the summer of 2006. D. geminata abundance decreased in Boulder Creek after an unusual flood event caused by 3 days of sustained rainfall in the headwaters of the watershed. However, within a week, coverage had been restored to pre-flood levels. Variations in D. geminata abundance among sites were found to be negatively correlated with total dissolved phosphorus concentrations and bed movement, as measured by Shields stress. In contrast, D. geminata abundance was not significantly correlated with temperature, conductivity, pH, total suspended solids, or dissolved inorganic nitrogen. Our results suggest that bed movement may be a dominant scouring mechanism that acts to control the growth and distribution of D. geminata. The potential role of total dissolved phosphorus and bed movement in decreasing D. geminata coverage adds to the limited base of knowledge regarding controls on the growth and distribution of this species, and could be investigated by researchers studying D. geminata blooms in other stream ecosystems