Effects of late-season sheep grazing following early-season steer grazing on population dynamics of sericea lespedeza in the Kansas Flint Hills.

Mature ewes were used in a 4-yr study to evaluate effects of intensive late-season sheep grazing on vigor of sericea lespedeza in native tallgrass prairie. Pastures (N = 8; 31 ± 3.6 ha) infested with sericea lespedeza (initial basal frequency = 1.4%) were assigned randomly to one of two treatments: early-season beef steer grazing (1.1 ha/steer; initial BW = 258 ± 34 kg) from April 15 to July 15 followed by no grazing for the rest of the year (control; STR) or steer grazing from April 15 to July 15 followed by intensive grazing by mature ewes (0.2 ha/ewe; SHP) from August 1 to October 1. Ewes (initial BW = 65 ± 3.1 kg) were assigned randomly to graze four of eight pastures; remaining pastures were not grazed from August 1 to October 1. Vegetation responses to treatment were measured along four permanent 100-m transects in each pasture. Herbivory on sericea lespedeza was monitored weekly in each pasture from July 21 to October 7. Herbivory on sericea lespedeza in SHP and STR after steer grazing and before sheep grazing was not different (P = 0.51). In contrast, sericea lespedeza herbivory following sheep grazing was greater (P < 0.01) in SHP than in STR. Herbivory of individual sericea plants was greater (P < 0.01) in SHP than in STR by the end of week 1 of the sheep-grazing period (10.6% vs. 0.5%); moreover, herbivory on sericea lespedeza steadily increased (P ≤ 0.01) such that 92.1% of sericea lespedeza plants were grazed in SHP compared to 1.4% in STR by week 8 of the sheep-grazing period. Whole-plant DM weight of sericea lespedeza at dormancy was less (P < 0.01) in SHP than in STR. Additionally, annual seed production by sericea lespedeza was less (P < 0.01) in SHP than in STR (114 vs. 864 seeds/plant). Pasture forage biomass was not different (P = 0.76) between SHP and STR after the steer-grazing period. Conversely, STR had more (P < 0.01) residual forage biomass than SHP at the end of the sheep-grazing period. Growth performance of beef steers grazing from April 15 to July 15 annually was not different (P ≥ 0.59) between treatments. Our results were interpreted to suggest that intensive late-season grazing by sheep decreased vigor of sericea lespedeza. Late-season sheep grazing decreased forage biomass by 904 kg DM/ha compared with late-season rest; however, residual biomass was adequate to prevent soil-moisture loss and erosion during the dormant season.

Effects of prescribed fire timing on grazing performance of yearling beef cattle, forage biomass accumulation, and plant community characteristics on native tallgrass prairie in the Kansas Flint Hills.

Recent research demonstrated that mid- or late-summer prescribed fires can be employed to manage sericea lespedeza (Lespedeza cuneata) infestations in the Kansas Flint Hills. The effects of prescribed fire applied during the growing season (i.e., August to October) on grazing performance of yearling cattle have not been evaluated. Native pastures (n = 18; 22 ± 4.0 ha) were grouped by watershed and assigned randomly to one of three prescribed-fire treatments: spring (7 April ± 2.1 d), summer (21 August ± 5.7 d), or autumn (2 October ± 9.9 d). Yearling beef cattle were grazed from May to August at a targeted stocking density of 280 kg live-weight/ha following prescribed-fire application. Forage biomass accumulations, soil cover, plant species composition, and root carbohydrate concentrations in four native plant species were evaluated. Total body weight (BW) gains and average daily gain were greater (P = 0.01) for cattle that grazed the spring and summer prescribed-fire treatments compared with those that grazed the autumn prescribed-fire treatment. As a result, final BW were greater (P = 0.04) in the spring and summer treatments than the autumn treatment. Conversely, forage biomass accumulations did not differ (P = 0.91) between fire regimes. Proportions of bare soil were greater (P < 0.01) in the spring treatment compared with the summer and autumn treatments, whereas proportions of litter on the soil surface were greater (P < 0.01) in summer- and autumn-burned pastures compared with spring-burned pastures. Total basal cover of graminoids and forbs did not differ (P ≤ 0.15) between prescribed fire treatments. Likewise, total basal cover of C3 or C4 perennial grasses did not differ (P ≥ 0.23) between prescribed-fire treatments. No treatment differences (P = 0.24) in root starch or root water-soluble carbohydrate concentrations in big bluestem (Andropogon gerardii), little bluestem (Schizachyrium scoparium), Indiangrass (Sorghastrum nutans), or purple prairieclover (Dalea purpurea) were detected. These data were interpreted to suggest that summer or autumn prescribed fire can be applied without reducing forage biomass accumulations, root carbohydrate concentrations in key native plant species, or considerably altering native plant populations compared with conventional spring-season prescribed fire; however, summer prescribed fire could be favored over spring or autumn prescribed fire both to maintain stocker cattle growth performance and to achieve control over sericea lespedeza.

Effects of prescribed fire timing on vigor of the invasive forb sericea lespedeza (Lespedeza cuneata), total forage biomass accumulation, plant-community composition, and native fauna on tallgrass prairie in the Kansas Flint Hills.

The predominant grazing-management practice of the Kansas Flint Hills involves annual prescribed burning in March or April with postfire grazing by yearling beef cattle at a high stocking density from April to August. There has been a dramatic increase in sericea lespedeza (Lespedeza cuneata [Dumont] G. Don) coincident with this temporally focused use of prescribed fire in the Flint Hills region. The species is an aggressive invader and a statewide noxious weed in Kansas. Control has generally been attempted using repeated herbicide applications. This approach has not limited proliferation of sericea lespedeza and resulted in collateral damage to nontarget flora and fauna. Alternative timing of prescribed fire has not been evaluated for its control. Our objectives for this 4-yr experiment were to (1) document the effects of prescribed burning during early April, early August, or early September on vigor of sericea lespedeza, standing forage biomass, and basal cover of native graminoids, forbs, and shrubs and (2) measure responses to fire regimes by grassland bird and butterfly communities. Whole-plant dry mass, basal cover, and seed production of sericea lespedeza were markedly less (P < 0.01) in areas treated with prescribed fire in August or September compared with April. Forage biomass did not differ (P ≥ 0.43) among treatments when measured during July; moreover, frequencies of bare soil, litter, and total basal plant cover were not different (P ≥ 0.29) among treatments. Combined basal covers of C4 grasses, C3 grasses, annual grasses, forbs, and shrubs also did not differ (P ≥ 0.11) between treatments. Densities of grasshopper sparrow (Ammodramus savannarum), dickcissel (Spiza americana), and eastern meadowlark (Sturnella magna) were not negatively affected (P > 0.10) by midsummer or late-summer fires relative to early-spring fires. There were no differences (P > 0.10) in densities of grassland-specialist butterfly species across fire regimes. Under the conditions of our experiment, prescribed burning during summer produced no detrimental effects on forage production, desirable nontarget plant species, grassland birds, or butterfly communities but had strong suppressive effects on sericea lespedeza. Additional research is warranted to investigate how to best incorporate late-summer prescribed fire into common grazing-management practices in the Kansas Flint Hills.

GDNF revisited: A novel mammalian cell-derived variant form of GDNF increases dopamine turnover and improves brain biodistribution.

Parkinson's disease (PD) is a disorder affecting dopamine neurons for which there is no cure. Glial cell line-derived neurotrophic factor (GDNF) and the closely related protein neurturin are two trophic factors with demonstrated neuroprotective and neurorestorative properties on dopamine neurons in multiple animal species. However, GDNF and neurturin Phase-2 clinical trials have failed to demonstrate a significant level of improvement over placebo controls. Insufficient drug distribution in the brain parenchyma has been proposed as a major contributing factor for the lack of clinical efficacy in the Phase-2 trial patients. To address this issue, a novel mammalian cell-derived variant form of GDNF (GDNFv) was designed to promote better tissue distribution by reducing its heparin binding to the extracellular matrix and key amino acids were substituted to enhance its chemical stability. Administration of this fully glycosylated GDNFv in the normal rat striatum increased dopamine turnover and produced significantly greater brain distribution than E. coli-produced wildtype GDNF (GDNFwt). Intrastriatal GDNFv also protected midbrain dopamine neuron function in 6-hydroxydopamine-lesioned rats. Studies conducted in normal adult rhesus macaques support that GDNFv was well tolerated in all animals and demonstrated a greater volume of distribution than GDNFwt in the brain following intrastriatal infusion. Importantly, favorable physiological activity of potential therapeutic value was maintained in this variant trophic factor with significant target activation in GDNFv recipients as indicated by dopamine turnover modulation. These data suggest that GDNFv may be a promising drug candidate for the treatment of PD. Additional studies are needed in non-human primates with dopamine depletion. This article is part of the Special Issue entitled 'Drug Repurposing: old molecules, new ways to fast track drug discovery and development for CNS disorders'.

Continuous intranigral infusion is not associated with observable behavioral deficits or marked pathology: a preclinical safety study.

OBJECTIVE A better understanding of the effects of chronically delivering compounds to the substantia nigra and nearby areas is important for the development of new therapeutic approaches to treat alpha-synucleinopathies, like Parkinson's disease. Whether chronic intranigral delivery of an infusate could be achieved without causing motor dysfunction or marked pathology remains unclear. The authors evaluated the tolerability of continuously delivering an infusate directly into the rhesus monkey substantia nigra via a programmable pump coupled to a novel intraparenchymal needle-tip catheter surgically implanted using MRI-guided techniques. METHODS The MRI contrast agent gadopentetate dimeglumine (Magnevist, 5 mM) was used to noninvasively evaluate catheter patency and infusion volume associated with 2 flow rates sequentially tested in each of 3 animals: 0.1 µl/min for 14 days into the right substantia nigra and 0.1 µl/min for 7 days plus 0.2 µl/min for an additional 7 days into the left substantia nigra. Flow rate tolerability was assessed via clinical observations and a microscopic examination of the striatum and midbrain regions. RESULTS Evaluation of postsurgical MRI indicated that all 6 catheters remained patent throughout the study and that the volume of distribution achieved in the left midbrain region at a rate of up to 0.2 µl/min (2052 ± 168 mm3) was greater than that achieved in the right midbrain region at a constant rate of 0.1 µl/min (1225 ± 273 mm3) by nearly 2-fold. Both flow rates provided sufficient infusate coverage of the rhesus (and possibly the human) midbrain region. There were no indications of observable deficits in behavior. Histopathological evaluations confirmed that all catheter tips were placed in or near the pars compacta region of the substantia nigra in all animals. There was no evidence of infection at any of the 6 catheter sites. Mild to moderate microglial reactions were observed at most catheter track sites and were comparable between the 2 infusion rates. Finally, there was neither observable decrease of tyrosine hydroxylase staining in the striatum nor detectable necrosis of neurons in the pars compacta region of the substantia nigra in any of the animals. CONCLUSIONS The data from this study support the feasibility of using a pump-and-catheter system for chronic intranigral infusion and lay the foundation for using this approach to treat Parkinson's disease or other related degenerative diseases that would benefit from targeted drug delivery to the substantia nigra or to other brainstem regions.

Right ventricular outflow tract reconstructive model in adult sheep.

Patients born with congenital right ventricular outflow tract lesions are faced with invasive procedures to establish hemodynamic and physiological stability. Commonly, multiple subsequent surgical procedures are required due to deterioration of a previous repair. These procedures carry additive risks of mortality and morbidity. Less aggressive procedures with accompanying lower risk is ideal. Success in percutaneously placing a transcatheter valve has previously been reported; however, continued safety and efficacy of any technique needs continual assessment. We developed a model for preclinical evaluation of a percutaneous placement of a pulmonic transcatheter valve in adult sheep, including preoperative, surgical, and postoperative techniques for long-term evaluation. Adult sheep were assessed and determined to be acceptable for study enrollment. Perioperative antibiotics and analgesics were given prior to a left thoracotomy. A Medtronic, Hancock 1 valve conduit was inserted for reconstruction of the right ventricular outflow tract. The Hancock 1 valve conduit alone represented the control group and the test animals comprised the addition of a Melodytrade mark transcatheter pulmonary valve (TPV), within the Hancock 1 valve conduit. Fifteen adult sheep survived the surgical implant procedure with no perioperative mortality. There were four early postoperative deaths, three due to infection and one due to heart failure, secondary to intraoperative heart block. The remaining 11 animals remained healthy, gained weight, and survived to termination at 5 months. An initial definite-sized valve conduit was implanted, followed by inserting a single size TPV, which allowed a more accurate physiological assessment of any chosen valve. Our developed adult sheep model for percutaneous TPV implantation for right ventricular outflow tract lesions was successful for long-term assessment by utilizing our preoperative, surgical, and postoperative techniques.

Flow characterization of the ADVANTAGE and St. Jude Medical bileaflet mechanical heart valves.

BACKGROUND AND AIM OF THE STUDY: The study aim was to characterize time-dependent flow fields and flow structures within the ADVANTAGE (ADV) and St. Jude Medical (SJM) prosthetic bileaflet mechanical heart valves. METHODS: Three-dimensional unsteady computational fluid dynamic simulations were conducted in the aortic position for both valves. Flow boundary conditions were acquired from an in-vitro experiment. The governing equations were solved by a finite volume method that employed a moving cell technique to simulate the motion of the valve leaflet in the cardiac cycle. The computed velocities were subsequently validated using the velocities measured in the in-vitro experiment. RESULTS: Both valves had similar flow phenomena at the geometric symmetry plane of the valve housing, and both experienced a waterhammer effect upon closure. However, flow characteristics in the pivots differed distinctively between both valves. More dynamic flow activity was observed at the bi-level butterfly pivots of the ADV valve. Flow vena contracta and large flow boundary separation zones at the central flow orifice were captured adjacent to the pivots of the SJM valve. During valve opening, retrograde systolic flow at the bottom of the pivot was observed. No persistent flow stases were seen in the pivots of either valves. CONCLUSION: Although overall flow characterization for both valves was similar, flow features within each valve's pivots correlated to the pivot design. The bi-level butterfly pivot design of the ADV valve appeared to provide relatively easy passages for pivot flow washing.

An in vitro assessment by means of laser Doppler velocimetry of the medtronic advantage bileaflet mechanical heart valve hinge flow.

OBJECTIVE: The aim of this study was to evaluate the hinge flow field characteristics of the Medtronic Advantage bileaflet valve and compare them with the flow fields of the St Jude Medical standard valve. The present study provides laser Doppler velocimetry results for the Advantage and St Jude Medical valves to make a direct comparison of the flow fields of the 2 valve designs. This study aids in determining the preclinical efficacy of Medtronic's new bileaflet valve hinge design. METHODS: Two-dimensional laser Doppler velocimetry was used to measure the velocities in the hinge regions of size 29 Medtronic Advantage and St Jude Medical standard bileaflet valve designs. Exact dimensional models of the bileaflet valves, including the hinge regions, were cast from transparent plastic materials to conduct these measurements under simulated physiologic conditions. Laser Doppler velocimetry measurements were conducted under physiologic conditions, with the valves placed in the mitral position of a pulsatile flow loop. Measurements were taken at several elevation levels in the hinge region. Multiple measurement locations obtained in each plane provided a grid work by which the flow fields could be detailed. RESULTS: Velocity measurements obtained for each valve design in the hinge recess were used to reconstruct the flow fields. For the Advantage valve, the peak velocities during leakage flow in the hinge at zero depth, one-third depth, and two-thirds depth levels into the hinge recess were 0.9, 1.6, and 1.8 m/s, respectively. Corresponding values for the St Jude Medical valve were 1.3, 1.6, and 2.1 m/s, respectively. From the reconstructed flow fields, the flow patterns seen within the 2 hinge designs exhibited similar features, with more dynamic flow patterns observed in the Advantage hinge during the forward flow phase. CONCLUSIONS: The present study demonstrated that the hinge flow dynamics of the Advantage bileaflet design were similar to those of the St Jude Medical hinge design. The velocities within the hinge were slightly higher for the St Jude Medical valve but not significantly different. There appears to be more dynamic flow through the hinge of the Advantage valve during the forward flow phase.

A numerical simulation of mechanical heart valve closure fluid dynamics.

A computational fluid dynamics model for the analysis of the bileaflet mechanical heart valve closure process is presented. The objective of the study is to demonstrate the ability of the numerical model to simulate the leaflet motion during the closing phase in order to investigate the closure fluid dynamics and to evaluate the effect of alterations in the leaflet tip geometry. The model has been applied to six different combinations of the leaflet tip geometry and the gap width between the leaflet tip and the housing. The results show that the negative pressure quickly develops on the atrial side of the leaflet tip. The pressure becomes more negative as the leaflet closure progresses and the lowest pressure is reached before the leaflet comes to a stop in the closed position. The flow dynamics at the instant of valve closure is strongly dependent on the leaflet velocity during the closing phase. Decrease of the tip velocity by a factor of three in the last four degrees of leaflet motion leads to a 50% reduction in the negative pressure magnitude.