32 research outputs found
Targeted PEG-poly(glutamic acid) complexes for inhalation protein delivery to the lung
Pulmonary delivery is increasingly seen as an attractive, non-invasive route for the delivery of forthcoming protein therapeutics. In this context, here we describe protein complexes with a new ‘complexing excipient’ - vitamin B12-targeted poly(ethylene glycol)-block-poly(glutamic acid) copolymers. These form complexes in sub-200 nm size with a model protein, suitable for cellular targeting and intracellular delivery. Initially we confirmed expression of vitamin B12-internalization receptor (CD320) by Calu-3 cells of the in vitro lung epithelial model used, and demonstrated enhanced B12 receptor-mediated cellular internalization of B12-targeted complexes, relative to non-targeted counterparts or protein alone. To develop an inhalation formulation, the protein complexes were spray dried adopting a standard protocol into powders with aerodynamic diameter within the suitable range for lower airway deposition. The cellular internalization of targeted complexes from dry powders applied directly to Calu-3 model was found to be 2–3 fold higher compared to non-targeted complexes. The copolymer complexes show no complement activation, and in vivo lung tolerance studies demonstrated that repeated administration of formulated dry powders over a 3 week period in healthy BALB/c mice induced no significant toxicity or indications of lung inflammation, as assessed by cell population count and quantification of IL-1β, IL-6, and TNF-α pro-inflammatory markers. Importantly, the in vivo data appear to suggest that B12-targeted polymer complexes administered as dry powder enhance lung retention of their protein payload, relative to protein alone and non-targeted counterparts. Taken together, our data illustrate the potential developability of novel B12-targeted poly(ethylene glycol)-poly(glutamic acid) copolymers as excipients suitable to be formulated into a dry powder product for the inhalation delivery of proteins, with no significant lung toxicity, and with enhanced protein retention at their in vivo target tissue
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An Evaluation of Grazing Intensity Influences on California Annual Range
Influences of grazing intensity on species composition and herbage production of grass-woodland and improved grassland subtypes of annual range were evaluated over a 5-year period in coastal northern California using 3 grazing treatments (100, 150, and 200% of moderate stocking). Herbage utilization did not differ significantly between the 2 subtypes but averaged 42, 52, and 69% for the respective treatments. Plant species and production responses differed significantly between woodland and grassland subtypes. On woodland, ripgut brome (Bromus rigidus Roth.) and wild oats (Avena barbata Brot. and A. fatua L.) were most sensitive to grazing intensity while wild barley (Hordeum leporinum Link. and H. hystrix Roth.) and annual fescue (Festuca dertonensis (all.) Asch. and Graebn. and F. megalura Nutt.) were least sensitive. On improved grassland, subterranean clover (Trifolium subterraneum L.) increased and soft chess (Bromus mollis L.) decreased with increasing grazing intensity. Soft chess remained most plentiful on woodland range under heaviest grazing and it continued to be a major species under heavy grazing of grassland, demonstrating tolerance to grazing intensity. Filaree (Erodium cicutarium (L.) L'Her. and E. botrys (Cav.) Bertol.) declined on woodland but increased on grassland as grazing intensified. Peak standing crop was not significantly affected by grazing intensity on woodland range but was greatest at 150% of moderate stocking and lowest at 200% of moderate stocking on grassland range. Decline in grassland herbage yield under heaviest grazing was due to reduction of soft chess which was displaced by subterranean clover. Effects of grazing intensity on range composition and productivity were confounded by innate differences in ranges and yearly weather patterns. Herbage production was impacted more by annual growing conditions than by grazing regimens, but there was no correlation between total annual precipitation and peak standing crop.This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202
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Nutrient Content of Sheep Diets on a Serpentine Barrens Range Site
Nutritional composition of sheep diets from a serpentine barrens range site was determined at various seasons and stages of plant growth and compared to diets from 3 other annual range sites. Sheep diets from the serpentine site tended to be more nutritious, ranking in the highest pair of sites in digestibility, digestible energy, crude protein, and ether extract, and containing highest concentrations of magnesium. These differences were subtle and had limited application to management. Nutritional differences attributable to plant phenology were inconsistent but more dramatic than those due to site. Late summer and winter were potentially critical periods for brood ewes with protein and energy, respectively, likely to be marginal or possibly deficient. Contents of nutrients and nutritional properties did not differ between available herbage and forage selected by sheep from serpentine barrens.This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202
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Cattle Diets on Semidesert Grassland: Nutritive Content
A study of chemical composition and organic matter digestibility of cattle diets was conducted on semidesert grassland in southern New Mexico during different seasons. Forage quality was highest in the spring. Fall diets were lower in digestibility, contained less crude protein and the least estimated digestible energy. Level of protein in fall diets was greater than requirements for dry cows but was less than recommended levels for lactating cows or growing calves. A stepwise regression equation showed that protein accounted for more variation in in vitro digestibility than did other components.This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202
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Cattle Diets on Semidesert Grassland: Botanical Composition
Botanical composition of cattle diets on semidesert rangeland was studied by microhistological techniques. Cattle consumed 56% of all species available. Dietary portions of grasses, forbs, shrubs, and unidentifiable plants averaged 45, 32, 19, and 6%, respectively. Composition of diets changed with seasons. Grass contents of diets were highest in summer and lowest in spring. Mesa dropseed was the most common species in diets. Perennial grasses represented dependable sources of forage, but never comprised more than 50% of the steers' diets in any season, and should not be used as the sole criterion for estimating forage production or determining stocking rates. Shrub portions were highest in spring when soaptree yucca was grazed almost exclusively. Forb fractions of diets varied little among seasons but were highest in winter. Forbs and shrubs comprised over one-half of the diets in certain seasons and should be grazed in these seasons if full benefit is to be derived from them. Preference ranking of forage plants evaluated selectivity and palatability but preference trends were inconsistent and most affected by species availability.This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202
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Forage Intake in Two-Year Old Cows and Heifers Grazing Blue Grama Summer Range
Forage intake was estimated in 2-year-old cows and 2-year-old heifers grazing blue grama summer range by using the fecal output-indigestibility ratio technique. Heifers consumed only 67% as much forage as cows (1.4 vs 2.1 percent of body weight). Forage intake by cows was greater in earlier stages of lactation than in later stages (2.5% of body weight at 90 days postpartum vs 1.7% of body weight at 150 days postpartum). Considerable variation occurred in estimated levels of intake.This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202
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Accuracy of Roughage Intake Estimations as Determined by a Chromic Oxide-In Vitro Digestibility Technique
Intakes of roughage rations by two-year-old cows and heifers were estimated by a chromic oxide dilution technique and compared against actual measured levels of intake. Intake was overestimated 2.9 percent in cows and 28.6 percent in heifers. Linear regression was used to increase accuracy of intake estimates by developing equations to predict actual intake from values obtained by the indicator dilution approach. A system for using this approach under range conditions was suggested. It was shown that non-adjusted intake estimates were not absolute values and the assumption that estimated intake values are relative and adequate for comparison is valid only when ruminants consume similar diets.This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202