Experimental observations and numerical modeling of lipid-shell microbubbles with calcium-adhering moieties for minimally-invasive treatment of urinary stones

A novel treatment modality incorporating calcium-adhering microbubbles has recently entered human clinical trials as a new minimally-invasive approach to treat urinary stones. In this treatment method, lipid-shell gas-core microbubbles can be introduced into the urinary tract through a catheter. Lipid moities with calcium-adherance properties incorporated into the lipid shell facilitate binding to stones. The microbubbles can be excited by an extracorporeal source of quasi-collimated ultrasound. Alternatively, the microbubbles can be excited by an intraluminal source, such as a fiber-optic laser. With either excitation technique, calcium-adhering microbubbles can significantly increase rates of erosion, pitting, and fragmentation of stones. We report here on new experiments using high-speed photography to characterize microbubble expansion and collapse. The bubble geometry observed in the experiments was used as one of the initial shapes for the numerical modeling. The modeling showed that the bubble dynamics strongly depends on bubble shape and stand-off distance. For the experimentally observed shape of microbubbles, the numerical modeling showed that the collapse of the microbubbles was associated with pressure increases of some two-to-three orders of magnitude compared to the excitation source pressures. This in-vitro study provides key insights into the use of microbubbles with calcium-adhering moieties in treatment of urinary stones

Birth and early evolution of a planetary nebula

The final expulsion of gas by a star as it forms a planetary nebula --- the ionized shell of gas often observed surrounding a young white dwarf --- is one of the most poorly understood stages of stellar evolution. Such nebulae form extremely rapidly (about 100 years for the ionization) and so the formation process is inherently difficult to observe. Particularly puzzling is how a spherical star can produce a highly asymmetric nebula with collimated outflows. Here we report optical observations of the Stingray Nebula which has become an ionized planetary nebula within the past few decades. We find that the collimated outflows are already evident, and we have identified the nebular structure that focuses the outflows. We have also found a companion star, reinforcing previous suspicions that binary companions play an important role in shaping planetary nebulae and changing the direction of successive outflows.Comment: 9 pages + 3 figures. To appear in Nature, 2 April 199

Comparison Of Reionization Models: Radiative Transfer Simulations And Approximate, Semi-Numeric Models

We compare the predictions of four different algorithms for the distribution of ionized gas during the Epoch of Reionization. These algorithms are all used to run a 100 Mpc/h simulation of reionization with the same initial conditions. Two of the algorithms are state-of-the-art ray-tracing radiative transfer codes that use disparate methods to calculate the ionization history. The other two algorithms are fast but more approximate schemes based on iterative application of a smoothing filter to the underlying source and density fields. We compare these algorithms' resulting ionization and 21 cm fields using several different statistical measures. The two radiative transfer schemes are in excellent agreement with each other (with the cross-correlation coefficient of the ionization fields >0.8 for k < 10 h/Mpc and in good agreement with the analytic schemes (>0.6 for k < 1 h/Mpc). When used to predict the 21cm power spectrum at different times during reionization, all ionization algorithms agree with one another at the 10s of percent level. This agreement suggests that the different approximations involved in the ray tracing algorithms are sensible and that semi-numerical schemes provide a numerically-inexpensive, yet fairly accurate, description of the reionization process.Comment: 13 pages, 10 figure

An HST Snapshot Survey of Proto-Planetary Nebulae Candidates: Two Types of Axisymmetric Reflection Nebulosities

We report the results from an optical imaging survey of proto-planetary nebula candidates using the HST. We exploited the high resolving power and wide dynamic range of HST and detected nebulosities in 21 of 27 sources. All detected reflection nebulosities show elongation, and the nebula morphology bifurcates depending on the degree of the central star obscuration. The Star-Obvious Low-level-Elongated (SOLE) nebulae show a bright central star embedded in a faint, extended nebulosity, whereas the DUst-Prominent Longitudinally-EXtended (DUPLEX) nebulae have remarkable bipolar structure with a completely or partially obscured central star. The intrinsic axisymmetry of these proto-planetary nebula reflection nebulosities demonstrates that the axisymmetry frequently found in planetary nebulae predates the proto-planetary nebula phase, confirming previous independent results. We suggest that axisymmetry in proto-planetary nebulae is created by an equatorially enhanced superwind at the end of the asymptotic giant branch phase. We discuss that the apparent morphological dichotomy is caused by a difference in the optical thickness of the circumstellar dust/gas shell with a differing equator-to-pole density contrast. Moreover, we show that SOLE and DUPLEX nebulae are physically distinct types of proto-planetary nebulae, with a suggestion that higher mass progenitor AGB stars are more likely to become DUPLEX proto-planetary nebulae.Comment: 27 pages (w/ aaspp4.sty), 6 e/ps figures, 4 tables (w/ apjpt4.sty). Data images are available via ADIL (http://imagelib.ncsa.uiuc.edu/document/99.TU.01) To be published in Ap

Elemental Content of Calcium Oxalate Stones from a Canine Model of Urinary Stone Disease.

One of the most common types of urinary stones formed in humans and some other mammals is composed of calcium oxalate in ordered hydrated crystals. Many studies have reported a range of metals other than calcium in human stones, but few have looked at stones from animal models such as the dog. Therefore, we determined the elemental profile of canine calcium oxalate urinary stones and compared it to reported values from human stones. The content of 19 elements spanning 7-orders of magnitude was quantified in calcium oxalate stones from 53 dogs. The elemental profile of the canine stones was highly overlapping with human stones, indicating similar inorganic composition. Correlation and cluster analysis was then performed on the elemental profile from canine stones to evaluate associations between the elements and test for potential subgrouping based on elemental content. No correlations were observed with the most abundant metal calcium. However, magnesium and sulfur content correlated with the mineral hydration form, while phosphorous and zinc content correlated with the neuter status of the dog. Inter-elemental correlation analysis indicated strong associations between barium, phosphorous, and zinc content. Additionally, cluster analysis revealed subgroups within the stones that were also based primarily on barium, phosphorous, and zinc. These data support the use of the dog as a model to study the effects of trace metal homeostasis in urinary stone disease

Oncostatin M causes VEGF release from human airway smooth muscle: synergy with IL-1β

Vascular endothelial growth factor (VEGF), a potent angiogenesis factor, likely contributes to airway remodeling in asthma. We sought to examine the effects and mechanism of action of IL-6 family cytokines on VEGF release from human airway smooth muscle (HASM) cells. Oncostatin M (OSM), but not other IL-6 family cytokines, increased VEGF release, and IL-1beta enhanced OSM-induced VEGF release. OSM increased VEGF mRNA expression and VEGF promoter activity, whereas IL-1beta had no effect. IL-1beta did not augment the effects of OSM on VEGF promoter activity but did augment OSM-induced VEGF mRNA expression and mRNA stability. The STAT3 inhibitor piceatannol decreased both OSM-induced VEGF release and synergy between OSM and IL-1beta, without affecting responses to IL-1beta alone. Piceatannol also inhibited OSM-induced VEGF mRNA expression. In contrast, inhibitors of MAPK pathway had no effect on OSM or OSM plus IL-1beta-induced VEGF release. OSM increased type 1 IL-1 receptor (IL-1R1) mRNA expression, as measured by real-time PCR, and piceatannol attenuated this response. Consistent with the increase in IL-1R1 expression, OSM markedly augmented IL-1beta-induced VEGF, MCP-1, and IL-6 release. In summary, our data indicate OSM causes VEGF expression in HASM cells by a transcriptional mechanism involving STAT3. IL-1beta also synergizes with OSM to increase VEGF release, likely as a result of effects of IL-1beta on VEGF mRNA stability as well as effects of OSM on IL-1R1 expression. This is the first description of a role for OSM on IL-1R1 expression in any cell type. OSM may contribute to airway remodeling observed in chronic airway disease

Oncostatin M causes eotaxin-1 release from airway smooth muscle: synergy with IL-4 and IL-13.

BACKGROUND: Eotaxin is implicated in asthmatic eosinophilia. Oncostatin M (OSM) causes eotaxin release from fibroblasts. OBJECTIVE: We sought to examine the effects and mechanism of action of OSM and other IL-6 family cytokines on eotaxin release from human airway smooth muscle cells. METHODS: Eotaxin 1 release was measured by means of ELISA. Western blotting was used to examine mitogen-activated protein kinase and signal transducer and activator of transcription 3 (STAT-3) phosphorylation. Eotaxin promoter activity was analyzed in cells transfected with wild-type STAT-3, a mutant form of STAT-3 that cannot be phosphorylated, and a constitutively active form of STAT-3. The mRNA and protein expression of IL-4R alpha, the signaling receptor for IL-4 and IL-13, was evaluated by means of real-time PCR and flow cytometry, respectively. RESULTS: OSM increased eotaxin 1 release and augmented IL-4- or IL-13-induced eotaxin release, whereas other IL-6 family cytokines did not. OSM caused a greater increase in STAT-3 phosphorylation and STAT-3-mediated gene transcription than other IL-6 family cytokines. OSM increased eotaxin promoter activity and augmented IL-13- and IL-4-induced increases in promoter activity. The constitutively active form of STAT-3 increased eotaxin promoter activity, whereas the mutant form of STAT-3 that cannot be phosphorylated significantly reduced eotaxin promoter activity induced by OSM or IL-4 plus OSM. OSM increased IL-4R alpha mRNA and protein levels. CONCLUSIONS: OSM induces eotaxin 1 expression in human airway smooth muscle cells by a mechanism involving STAT-3. OSM synergizes with IL-13 and IL-4 to increase eotaxin 1 expression, possibly as a result of effects on IL-4R alpha expression

Elemental Content of Calcium Oxalate Stones from a Canine Model of Urinary Stone Disease

<div><p>One of the most common types of urinary stones formed in humans and some other mammals is composed of calcium oxalate in ordered hydrated crystals. Many studies have reported a range of metals other than calcium in human stones, but few have looked at stones from animal models such as the dog. Therefore, we determined the elemental profile of canine calcium oxalate urinary stones and compared it to reported values from human stones. The content of 19 elements spanning 7-orders of magnitude was quantified in calcium oxalate stones from 53 dogs. The elemental profile of the canine stones was highly overlapping with human stones, indicating similar inorganic composition. Correlation and cluster analysis was then performed on the elemental profile from canine stones to evaluate associations between the elements and test for potential subgrouping based on elemental content. No correlations were observed with the most abundant metal calcium. However, magnesium and sulfur content correlated with the mineral hydration form, while phosphorous and zinc content correlated with the neuter status of the dog. Inter-elemental correlation analysis indicated strong associations between barium, phosphorous, and zinc content. Additionally, cluster analysis revealed subgroups within the stones that were also based primarily on barium, phosphorous, and zinc. These data support the use of the dog as a model to study the effects of trace metal homeostasis in urinary stone disease.</p></div