Uptake, translocation, weathering and speciation of gold nanoparticles in potato, radish, carrot and lettuce crops.

Extensive use of nanomaterials in agriculture will inevitably lead to their release to the environment in significant loads. Thus, understanding the fate of nanoparticles in the soil-plant environment, and potential presence and consequent implication of nanoparticles in food and feed products, is required. We study plant uptake of gold nanoparticles from soil, and their distribution, translocation and speciation (in terms of particle size change and release of ionic Au) in the different plant tissues of four important crops (potato, radish, carrot and lettuce). Our new analytical protocol and experiments show the feasibility of determining the presence, concentration and distribution of nanoparticles in different plant parts, which differ from plant to plant. Critically, we identify the evident capacity of plants to break down (or substantially change the properties of) nanoparticles in the rhizosphere prior to uptake, as well as the evident capacity of plants to reorganize ionic metals as nanoparticles in their tissues. This could lead to nanoparticle exposure through consumption of crops.

Manganese-Enhanced MRI of the Brain in Healthy Volunteers.

BACKGROUND AND PURPOSE: The manganese ion is used as an intracellular MR imaging contrast agent to study neuronal function in animal models, but it remains unclear whether manganese-enhanced MR imaging can be similarly useful in humans. Using mangafodipir (Teslascan, a chelated manganese-based contrast agent that is FDA-approved), we evaluated the dynamics of manganese enhancement of the brain and glandular structures in the rostral head and neck in healthy volunteers. MATERIALS AND METHODS: We administered mangafodipir intravenously at a rate of 1 mL/minute for a total dose of 5 µmol/kg body weight. Nine healthy adult volunteers (6 men/3 women; median age, 43 years) completed baseline history and physical examination, 3T MR imaging, and blood work. MR imaging also followed mangafodipir administration at various time points from immediate to 7 days, with delayed scans at 1-3 months. RESULTS: The choroid plexus and anterior pituitary gland enhanced within 10 minutes of infusion, with enhancement persisting up to 7 and 30 days, respectively. Exocrine (parotid, submandibular, sublingual, and lacrimal) glands also enhanced avidly as early as 1 hour postadministration, generally resolving by 1 month; 3 volunteers had residual exocrine gland enhancement, which resolved by 2 months in 1 and by 3 months in the other 2. Mangafodipir did not affect clinical parameters, laboratory values, or T1-weighted signal in the basal ganglia. CONCLUSIONS: Manganese ions released from mangafodipir successfully enable noninvasive visualization of intra- and extracranial structures that lie outside the blood-brain barrier without adverse clinical effects, setting the stage for future neuroradiologic investigation in disease.

Validation of structural and functional lesions of diabetic retinopathy in mice.

Diabetic retinopathy is a serious long-term complication of diabetes mellitus. There is considerable interest in using mouse models, which can be genetically modified, to understand how retinopathy develops and can be inhibited. Not all retinal lesions that develop in diabetic patients have been reproduced in diabetic mice; conversely, not all abnormalities found in diabetic mice have been studied or identified in diabetic patients. Thus, it is important to recognize which structural and functional abnormalities that develop in diabetic mice have been validated against the lesions that characteristically develop in diabetic patients. Those lesions that have been observed to develop in the mouse models to date are predominantly characteristic of the early stages of retinopathy. Identification of new therapeutic ways to inhibit these early lesions is expected to help inhibit progression to more advanced and clinically important stages of retinopathy.

Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes.

AIMS/HYPOTHESIS: Diabetes results in the upregulation of the production of several components of the inflammatory response in the retina, including inducible nitric oxide synthase (iNOS). The aim of this study was to investigate the role of iNOS in the pathogenesis of the early stages of diabetic retinopathy using iNOS-deficient mice (iNos (-/-)). MATERIALS AND METHODS: iNos (-/-) mice and wild-type (WT; C57BL/6J) mice were made diabetic with streptozotocin or kept as non-diabetic controls. Mice were killed at different time points after the induction of diabetes for assessment of vascular histopathology, cell loss in the ganglion cell layer (GCL), retinal thickness, and biochemical and physiological abnormalities. RESULTS: The concentrations of nitric oxide, nitration of proteins, poly(ADP-ribose) (PAR)-modified proteins, endothelial nitric oxide synthase, prostaglandin E(2), superoxide and leucostasis were significantly (p < 0.05) increased in retinas of WT mice diabetic for 2 months compared with non-diabetic WT mice. All of these abnormalities except PAR-modified proteins in retinas were inhibited (p < 0.05) in diabetic iNos (-/-) mice. The number of acellular capillaries and pericyte ghosts was significantly increased in retinas from WT mice diabetic for 9 months compared with non-diabetic WT controls, these increases being significantly inhibited in diabetic iNos (-/-) mice (p < 0.05 for all). Retinas from WT diabetic mice were significantly thinner than those from their non-diabetic controls, whereas diabetic iNos (-/-) mice were protected from this abnormality. We found no evidence of cell loss in the GCL of diabetic WT or iNos (-/-) mice. Deletion of iNos had no beneficial effect on diabetes-induced abnormalities on the electroretinogram. CONCLUSIONS/INTERPRETATION: We demonstrate that the inflammatory enzyme iNOS plays an important role in the pathogenesis of vascular lesions characteristic of the early stages of diabetic retinopathy in mice.

Advective transport in the percolation backbone in two dimensions.

We show that, in the case of advective transport on the percolation backbone, the relevant structure below the correlation length is an ensemble of tortuous paths, rather than the classical links-nodes-blobs system. These paths are embedded in the few largest blobs that dominate the structure of the backbone. We find numerically that the mean particle displacement differs from the prediction given by classical finite-size scaling arguments. We also show that because of the complex velocity distribution between the paths, the mean first-passage time of the particles cannot be inferred directly from the mean particle displacement.

Correction of early subnormal superior hemiretinal DeltaPO(2) predicts therapeutic efficacy in experimental diabetic retinopathy.

PURPOSE: To test the hypothesis that regional retinal oxygenation responses to a hyperoxic inhalation challenge are associated with reported retinopathy outcomes after different therapies in rat models of diabetic retinopathy. METHODS: Six groups of rats were maintained for 3 months: controls (n = 8), untreated diabetic (n = 8), aminoguanidine (AMG)-treated diabetic (2.5 g/kg of diet; n = 6), untreated galactosemic (n = 7), AMG-treated galactosemic (n = 10), and WAY-509-treated (25 mg/kg body weight per day) galactosemic (n = 7). After 3 months, the change in oxygen tension was measured noninvasively from the superior to the inferior ora serrata, using a novel functional magnetic resonance imaging (fMRI) technique and a carbogen (a gas mixture of 5% carbon dioxide and 95% oxygen that has been used clinically, instead of 100% oxygen, to minimize the vasoconstrictive effects of pure O(2) on retinal blood flow and oxygenation) inhalation challenge. Retinal morphometric measurements were also obtained. RESULTS: Retinal lesions (acellular capillaries and pericyte ghosts) were not significantly (P > 0.05) present at 3 months in any experimental groups compared with the control group. Superior but not inferior hemiretinal change in partial pressure of oxygen (DeltaPO(2)) became significantly subnormal (P < 0.05) at 3 months of diabetes or galactosemia. Aminoguanidine, which has been found to inhibit the development of retinopathy in diabetic but not galactosemic rats, inhibited the development of a subnormal DeltaPO(2) in diabetes but not in galactosemia. WAY-509, which has been reported to inhibit retinopathy in galactosemic rats, inhibited the DeltaPO(2) defect in galactosemic rats. CONCLUSIONS: An early subnormal superior hemiretinal DeltaPO(2) after treatment appears to be a good predictor of the risk of development of retinopathy, as well as for assessing therapeutic efficacy in experimental diabetic retinopathy.

Variable supplemental oxygen during recovery does not reduce retinal neovascular severity in experimental ROP.

PURPOSE: To test the hypothesis that variable supplemental oxygen (VSO) during recovery is not as effective as constant supplemental oxygen treatment at reducing retinal neovascular severity in the newborn rat model of retinopathy of prematurity (ROP). METHODS: The ROP model consists of raising newborn rats in variable oxygen for 14 days and then allowing them to recover during the next 6 days (until day 20). During this recovery period, two VSO protocols were examined: 1) 24 hr cycled (28% for 24 hr and 21% for 24 hr) as a control, and 2) interrupted (28% for 23.75 hr and 21% for 0.25 hr). On day 20, retinas from both eyes of each animal were dissected, stained with ADPase, and analyzed for neovascular (NV) incidence, severity, and peripheral avascularity. RESULTS: No significant differences (P > 0.05) in NV incidence and severity were found between the 24 hr cycled (control) (95% (38/40), median 5 clockhrs, range 0.5-9, n = 38) and interrupted VSO groups (89% (40/45), 3.5 clockhrs, 0.5-10.5, n = 40). However, retinal NV severity from both VSO groups were significantly greater (P < 0.05) than that previously reported for constant supplemental oxygen treatment. Percent peripheral avascularities were not significantly different (P > 0.05) between the two VSO groups. CONCLUSIONS: These results support our hypothesis since both VSO conditions were significantly less effective at reducing retinal NV than constant supplemental oxygen during recovery. The possible application of these results to STOP-ROP trial is discussed.

Measuring the human retinal oxygenation response to a hyperoxic challenge using MRI: eliminating blinking artifacts and demonstrating proof of concept.

The retinal oxygenation response to a hyperoxic challenge measured using MRI appears to be an early and accurate marker of retinopathy risk in experimental models, with promising clinical potential. However, the application of this technique in humans is limited by blinking artifacts that can confound detection of subtle signal intensity changes. We asked subjects to refrain from blinking during a 12-s fast low-angle shot (FLASH) image, and to blink if needed during the following 3-s rest period. This no-blink blink cycle was repeated sequentially 20 times during either room-air or 100% oxygen breathing. Significant change (P < 0.05) was detected for the first time from the resultant blinking-artifact-free images in the preretinal vitreous oxygen tension (upper limit of about 13 mm Hg (1.8 KPa, N = 3)) following a 10-min hyperoxic inhalation challenge. These results provide the proof-of-concept data needed for future MRI evaluation of the retinal oxygenation response and human retinopathy, such as diabetic retinopathy.

Application of continuous time random walk theory to tracer test measurements in fractured and heterogeneous porous media.

We examine a set of analytical solutions based on the continuous time random walk (CTRW) approach, which can be evaluated numerically and used to analyze breakthrough data from tracer tests. Practical application of these solutions, with discussion of the physical meaning of the relevant model parameters, is emphasized. The CTRW theory accounts for the often observed non-Fickian (or scale-dependent) dispersion behavior that cannot be properly quantified by using the advection-dispersion equation. The solutions given here, valid for a wide range of dispersive behaviors of conservative tracers, and useful for both characterization and prediction, have been integrated into a library of external functions for use with the GRACE graphical display and analysis package. Example applications of these solutions are presented. The library and graphics software are freely accessible from a Web site.

Studying the outcomes of community-based coalitions.

Community-based coalitions are popular structures for creating community benefits. But desired effects have been reported only for single cases, the overall documented evidence to date for positive coalition outcomes being weak. Methodological obstacles may account for much of the missing evidence, and research possibilities for addressing these obstacles are suggested. Alternative interpretations include the positions that coalitions in general are not effective intervention mechanisms, that traditional scientific methodology is poorly suited for capturing fine-grained coalition outcomes, and that coalitions and similar collaborative organizations are too complex to be adequately evaluated by the methodology that is now available.

Analysis of field observations of tracer transport in a fractured till.

We analyze a set of observations from a recently published, field-scale tracer test in a fractured till. These observations demonstrate a dominant, underlying non-Fickian behavior, which cannot be quantified using traditional modeling approaches. We use a continuous time random walk (CTRW) approach which thoroughly accounts for the measurements, and which is based on a physical picture of contaminant motion that is consistent with the geometric and hydraulic characterization of the fractured formation. We also incorporate convolution techniques in the CTRW theory, to consider transport between different regions containing distinct heterogeneity patterns. These results enhance the possibility that limitations in predicting non-Fickian modes of contaminant migration can be overcome.

MR studies of retinal oxygenation.

In this paper, we summarize the development and application of two novel magnetic resonance based measurements of retinal oxygenation in experimental models of retinopathy, including diabetic retinopathy and retinopathy of prematurity. We use 19F-NMR and a small (microl) perfluorocarbon drop positioned in the preretinal vitreous space to make PO2 measurement of the inner retina. In addition, we use magnetic resonance imaging (MRI) to accurately and non-invasively measure the change in the preretinal PO2 (DeltaPO2) following the shift from breathing room air to a hyperoxic inhalation challenge. The advantages and disadvantages of each method are discussed. New applications of these techniques in the newborn rat and adult mouse are presented. We expect such studies to motivate future MRI oxygenation studies of human retinopathy, including diabetic retinopathy and retinopathy of prematurity.

Preretinal neovascularization associated with acetazolamide-induced systemic acidosis in the neonatal rat.

PURPOSE: NH4Cl gavage in the neonatal rat produces a metabolic acidosis-induced retinopathy which serves as a model for retinopathy of prematurity (ROP). Acetazolamide induces a metabolic acidosis via an alternative biochemical mechanism (bicarbonate loss versus hydrogen ion load). In the present study, the following hypothesis was tested: acetazolamide-induced acidosis is associated with preretinal neovascularization in the neonatal rat. METHODS: All studies used newborn Sprague-Dawley rats raised in expanded litters of 25. Arterial blood pH was measured to determine the level of acidosis induced by intraperitoneal (IP) acetazolamide (50 or 200 mg/kg) or saline. In a separate retinopathy study, newborn rats (n = 75) were randomized to either IP acetazolamide, 50 mg/kg (low-dose), or IP saline twice daily from days 2 to 7. After 5 days of recovery, retinal vasculature was assessed using ADPase staining and light microscopy. The presence and severity (clock hours) of neovascularization were assessed by three masked observers. In an additional retinopathy study, newborn rats (n = 100) were randomized to either IP acetazolamide, 200 mg/kg (high-dose), or IP saline twice daily from days 2 to 7. After 5 days of recovery, the retinas were similarly analyzed. RESULTS: Neovascularization occurred in 59% of rats receiving high-dose acetazolamide (200 mg/kg). High-dose acetazolamide produced a severe acidosis (pH 7.13 +/- 0.06) during drug delivery. Low-dose acetazolamide (50 mg/kg) produced a pH (7.22 +/- 0.07) that was intermediate between high-dose (200 mg/kg) acetazolamide (P < 0.001) and saline controls (7.42 +/- 0.06, P < 0.001); however, neither low-dose acetazolamide nor saline induced preretinal neovascularization. CONCLUSIONS: Acidosis induced by high-dose acetazolamide, independent of hyperoxemia or hypoxemia, is associated with preretinal neovascularization in the neonatal rat. Induction of neovascularization appears to depend on a critical threshold of acidosis severity. This study further supports a proposed independent role for acidosis in the pathogenesis of ROP.

The effect of partial vitrectomy on blood-ocular barrier function in the rabbit.

PURPOSE: To compare ocular vascular permeability in the rabbit after vitrectomy as assessed by contrast-enhanced magnetic imaging (CE-MRI) and measurements of aqueous and vitreous humor protein concentration. METHODS: Partial vitrectomies were performed, irrigating with BSS or BSS PLUS. Post-operative vascular leakage was determined by CE-MRI following intravenous administration of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Aqueous and vitreous protein concentrations were quantified by standard biochemical assay. ERG evaluations were performed on postoperative days 1, 3, and 7. RESULTS: Using BSS as irrigant, breakdown of the inner blood-retinal barrier (BRB) occurred in 4/7 eyes on post-operative day 1. The rate of Gd-DTPA leakage was significantly greater on postoperative day 1 than that in unoperated, control eyes, but declined approximately 50% by day 3. At both time points, outer BRB breakdown was restricted to the sclerotomy wounds. No BRB leakage was detectable in control eyes. Blood-aqueous barrier (BAB) leakage was bilateral on day 1. Significantly greater Gd-DTPA leakage occurred in the operated eye than in the nonsurgical contralateral eye. On day 3, approximately 40% bilateral reduction in leakage indicated resolution of BAB leakage. Notably, Gd-DTPA leakage of the BAB and BRB was significantly reduced in the BSS PLUS treated group. In contrast to MRI assessments, protein concentrations of the aqueous and vitreous in the surgical eye showed no detectable differences between BSS and BSS PLUS. Concurrent with the transient loss of ocular barrier function, ERG responses also declined. However, by day 7 greater than 90% recovery was noted in BSS PLUS treated animals but not in the BSS treatment group. CONCLUSIONS: CE-MRI is capable of detecting subtle changes in vascular permeability following ocular surgery. Advantages of using BSS PLUS compared to BSS as the irrigating solution can be detected using this technique. BSS PLUS's protection of barrier function is consistent with a rapid recovery in retinal function not observed in BSS treated eyes.

The Community Tool Box: a Web-based resource for building healthier communities.

Building healthier cities and communities requires an array of community-building skills that are not always taught in formal education. The Community Tool Box (http://ctb.ukans.edu) is an Internet-based resource for practical, comprehensive, accessible, and user-friendly information on community-building, which both professionals and ordinary citizens can use in everyday practice. It connects people, ideas, and resources, offering more than 200 how-to sections and more than 5,000 pages of text.

Significant reduction of the panretinal oxygenation response after 28% supplemental oxygen recovery in experimental ROP.

PURPOSE: To test the hypothesis that after supplemental oxygen recovery (SOR) in the newborn rat model of retinopathy of prematurity (ROP) the preretinal neovascular (NV) incidence and severity are decreased and the panretinal oxygenation ability is improved. METHODS: Newborn rats were first raised in either room air (controls) or variable oxygen (50%/10%) for 14 days. The experimental rats were recovered during the next 6 days (until day 20) in either room air (21% O2) or supplemental oxygen (28%). All groups were then exposed to room air for an additional 6 days (until day 26). On day 20, magnetic resonance imaging (MRI) was used to determine the panretinal oxygenation response (deltaPO2, mm Hg) to a carbogen (95% O2/5% CO2) inhalation challenge. On days 20 and 26, the retinas from a different subset of control, room air-recovered, or SOR-recovered animals were analyzed using ADPase stained or fluorescein-labeled dextran infused retinal flatmounts. RESULTS: On day 20, the panretinal deltaPO2 of the room air-recovered group (125 +/- 5 mm Hg, mean +/- SEM, n = 12) was significantly (P < 0.05) lower than that of the control group (179 +/- 6 mm Hg, n = 11). The panretinal deltaPO2 value for the SOR group (87 +/- 5 mm Hg, n = 7) was significantly (P < 0.05) lower than both the room air-recovered group and the control group. The NV incidence and severity were significantly reduced (P < 0.05) in the SOR animals compared with the room air-recovered animals. In contrast, on day 26 (after 6 days in room air), the NV incidence was statistically (P < 0.05) greater in the animals that had been exposed to SOR compared with room air-recovered animals. CONCLUSIONS: After 28% SOR, the expected decrease in NV incidence and severity occurred but with an unexpected decrease in panretinal oxygenation ability. The present data strongly support an association between subnormal panretinal oxygenation ability and increased NV risk in the newborn rat ROP model. MRI appears to be a powerful new approach for quantitatively and noninvasively measuring retinal oxygenation and may be applicable to study other ischemic or ischemia-related retinopathies in addition to ROP, such as diabetic retinopathy, sickle cell retinopathy, macular degeneration, and glaucoma.

Collaboration for health improvement: models for state, community, and academic partnerships.

The value of approaching health improvement through collaborative models seems self-evident, especially at the community level. A review of the literature, however, reveals a number of challenges in terms of helping us understand precisely what it is that makes collaborative models effective in influencing health. The purpose of this article is to describe important elements of collaboration that state, local, and academic partners may wish to consider when developing models for health improvement. The author will provide examples of collaborative strategies that are emerging from the Turning Point: Collaborating for a New Century in Public Health initiative.

Subnormal retinal oxygenation response precedes diabetic-like retinopathy.

PURPOSE: Determining which patients are at risk for the development of diabetic retinopathy is expected to greatly improve existing prevention and treatment options. In this study, using an animal model of diabetic retinopathy, the hypothesis was tested that magnetic resonance imaging (MRI) and a carbogen inhalation challenge provides important diagnostic information regarding the risk of developing diabetic retinopathy. METHODS: MRI was used to measure noninvasively the change in oxygen tension along the entire inner retina (i.e., from superior ora serrata to inferior ora serrata) during a carbogen (95% O2/5% CO2) inhalation challenge (IOVS 1996;37:2089). Two animal groups were examined by this MRI method at two time points: (1) rats fed either normal rat chow (n = 20) or a 50% galactose diet (n = 20) for 3.5 months (i.e., before the appearance of extensive retinal lesions) or (2) rats fed either normal rat chow (n = 3) for 15 months or a 30% galactose diet (n = 4) for 15 to 18 months (i.e., when lesions are present). Retinal biochemical and morphometric measurements were also obtained. RESULTS: After 3.5 months of galactosemia, before the appearance of extensive retinal morphologic lesions, a significant (P < 0.05) reduction in the panretinal oxygenation response was observed in the galactosemic group compared with its age-matched control. These galactose-fed animals also displayed a significantly (P < 0.05) larger oxygenation response in the inferior hemiretina than in the superior hemiretina. After 15 to 18 months of galactosemia, during the period when lesions are present, the panretinal oxygenation response remained significantly (P < 0.05) lower in the galactose-fed animals than in their age-matched controls. In contrast to the 3.5-month results, the oxygenation response in galactosemic animals at 15 to 18 months was significantly (P < 0.05) larger in the superior than in the inferior hemiretina. Hemiretinal oxygenation responses were not different in normal controls at either duration. CONCLUSIONS: MRI measurement of the retinal oxygenation response to a carbogen challenge appears to be a powerful new and noninvasive approach that may be useful for assessing aspects of pathophysiology underlying the development of diabetic retinopathy in galactosemic rats. These results support our working hypothesis and suggest that further research into the diagnostic potential of this MRI approach for predicting the development of diabetic retinopathy is warranted.

Angiographic criteria reliably predict when carotid endarterectomy can be safely performed without a shunt.

BACKGROUND: Selective shunting during carotid endarterectomy is widely performed, but the optimal approach for predicting when a shunt is unnecessary remains uncertain. We evaluated the ability of preoperative cerebral angiography to predict when carotid endarterectomy could be safely performed without a shunt. STUDY DESIGN: Eighty-seven patients undergoing carotid endarterectomy between August 1991 and December 1997 had preoperative cerebral angiograms. The angiograms were evaluated for the presence of collateral flow from the contralateral carotid through the anterior communicating artery and from the posterior circulation through the posterior communicating artery. Patients then underwent endarterectomy and were selectively shunted based on somatosensory evoked potential changes. Internal carotid artery stump pressure was routinely measured in all patients. RESULTS: Nine patients (10%) had a shunt placed based on somatosensory evoked potential changes and none of the 87 patients had a perioperative (30 days) stroke. Angiography revealed that 36 patients (41%) had no cross-filling from the contralateral carotid through the anterior communicating artery. Nine of these patients (25%) required a shunt; none of the 51 patients with adequate cross-filling (p < 0.001) did. Furthermore, 94% of the patients without cross-filling but with a patent ipsilateral posterior communicating artery did not require a shunt using somatosensory evoked potential changes as the standard for shunt insertion. Stump pressure measurements (> or = 25 mmHg) or (> or = 50 mmHg) did not reliably exclude the need for a shunt. Only 2 of 15 patients with contralateral carotid occlusion and 1 of 16 patients with a prior ipsilateral stroke required shunts. CONCLUSIONS: In the presence of cross-filling from the contralateral carotid artery, shunt insertion was uniformly unnecessary. In addition, routine shunting of patients with previous ipsilateral strokes or contralateral carotid occlusion was not always necessary. Stump pressures were less sensitive than angiographic criteria in determining when a shunt was unnecessary. Evaluation of cross-filling from the contralateral carotid artery on preoperative angiography can predict with certainty which patients will not require a shunt.