Abstract
We use data from five stellar occultations observed between 2013 and 2016 to constrain Chariklo’s size and shape, and the ring reflectivity. We consider four possible models for Chariklo ...(sphere, Maclaurin spheroid, triaxial ellipsoid, and Jacobi ellipsoid), and we use a Bayesian approach to estimate the corresponding parameters. The spherical model has a radius
R
= 129 ± 3 km. The Maclaurin model has equatorial and polar radii
and
, respectively, with density
. The ellipsoidal model has semiaxes
,
, and
. Finally, the Jacobi model has semiaxes
a
= 157 ± 4 km,
b
= 139 ± 4 km, and
c
= 86 ± 1 km, and density
. Depending on the model, we obtain topographic features of 6–11 km, typical of Saturn icy satellites with similar size and density. We constrain Chariklo’s geometric albedo between 3.1% (sphere) and 4.9% (ellipsoid), while the ring
I
/
F
reflectivity is less constrained between 0.6% (Jacobi) and 8.9% (sphere). The ellipsoid model explains both the optical light curve and the long-term photometry variation of the system, giving a plausible value for the geometric albedo of the ring particles of 10%–15%. The derived mass of Chariklo of 6–8 × 10
18
kg places the rings close to 3:1 resonance between the ring mean motion and Chariklo’s rotation period.
We consider the formation of extreme mass-ratio inspirals (EMRIs) sourced from a stellar cusp centred on a primary supermassive black hole (SMBH) and perturbed by an inspiraling less massive ...secondary SMBH. The problem is approached numerically, assuming the stars are non-interacting over these short time-scales and performing an ensemble of restricted three-body integrations. From these simulations, we see that not only can EMRIs be produced during this process, but the dynamics are also quite rich. In particular, most of the EMRIs are produced through a process akin to the Kozai-Lidov mechanism, but with strong effects due to the non-Keplerian stellar potential, general relativity and non-secular oscillations in the angular momentum on the orbital time-scale of the binary SMBH system.
: It is generally accepted that activation of the innate immune system and increased release of pro‐inflammatory cytokines and other mediators plays an important role in the development of alcoholic ...liver disease (ALD). The mechanisms involved in the ethanol‐induced activation of monocytes/macrophages (including Kupffer cells) are however, still a matter of debate. The brief review will summarize the published data from the literature on the two main pathomechanisms discussed until now: I) Gut‐derived bacterial toxins, specially endotoxin; and II) metabolic changes induced by alcohol oxidation (independent of mechanism I). For pathomechanism I, clear evidence has been published from numerous groups: Alcohol induces mucosal injury in the upper gastrointestinal tract and leads to marked increase in the permeability of the gut mucosa to macromolecules such as endotoxin. The resulting endotoxemia then leads to activation of Kupffer cells and other macrophages. The increased release of pro‐inflammatory mediators (e.g., TNF‐α, Il‐1, reacting oxygen species) and infiltration of other inflammatory cells (e.g., neutrophils) finally causes liver damage. Regarding the second pathomechanism it has repeatedly been argued that the metabolic alterations which are induced by chronic administration of ethanol to rats or mice might increase the sensitivity of monocytes/macrophages to secrete TNF‐α and other pro‐inflammatory mediators thereby increasing the susceptibility to ethanol‐induced liver injury. However, in all feeding experiments the effect of ethanol on intestinal permeability and enhanced translocation of bacterial toxins (endotoxin) is likely to occur (or at least cannot be excluded). The latter holds true also for experiments using isolated macrophages/Kupffer cells from ethanol fed animals. Therefore, to clarify whether or not alterations related to ethanol metabolism (“direct” effects of ethanol) contribute to the activation of the innate immune system studies using germ‐free animals are needed to exclude the “indirect” effect of ethanol via gut‐derived bacterial toxins.
Effect of alcohol consumption on the gut Bode, Christiane; Christian Bode, J
Baillière's best practice & research. Clinical gastroenterology,
08/2003, Letnik:
17, Številka:
4
Journal Article
Recenzirano
Consumption of large quantities of alcoholic beverages leads to disturbances in the intestinal absorption of nutrients including several vitamins. The inhibition of the absorption of sodium and water ...caused by alcohol contributes to the tendency in alcoholics to develop diarrhoea. Excessive alcohol consumption (even a single episode) can result in duodenal erosions and bleeding and mucosal injury in the upper jejunum. An increased prevalence for bacterial overgrowth in the small intestine may contribute to functional and/or morphological abnormalities of this part of the gut and also to non-specific abdominal complaints in alcoholics. The mucosal damage caused by alcohol increases the permeability of the gut to macromolecules. This facilitates the translocation of endotoxin and other bacterial toxins from the gut lumen to the portal blood, thereby increasing the liver's exposure to these toxins and, consequently, the risk of liver injury. The results of recent experimental studies support the assumption that alcohol significantly modulates the mucosal immune system of the gut.
Organoids recapitulate the (patho)physiological processes in certain tissues and organs closer than classical cell lines. Therefore, organoid technology offers great potentials in drug development ...and testing, and personalized medicine. In particular, organoids can be used to study and predict drug-induced toxicity in certain tissues. However, until today few methods had been reported to analyze cell death in 3D-microtissues in a quantitative manner. Here, we describe a novel fluorometric method for the quantitative measurement of specific organoid cell death. Organoids are stained simultaneously with the cell impermeable nuclear dye propidium iodide and cell permeable Hoechst33342. While Hoechst allows in-well normalization to cell numbers, propidium iodide detects relative proportion of dead cells independent of hydrogel. Measurement and analysis time, as well as usability are drastically improved in comparison to other established methods. Parallel multiplexing of our method with established assays measuring mitochondrial activity further enhances its applicability in personalized medicine and drug discovery.
We developed a fluorometric method to quantify cell death in intestinal organoids based on DNA staining for normalization and cell permeability for cell death. The method, independent of cell number over a wide range, can be used to study toxic effects of drugs on intestinal organoids or other 3D microtissues, and can be combined with photometric assessment of mitochondrial respiration.
We find that the majority of systems hosting multiple tidal disruptions (TDs) are likely to contain hard binary supermassive black hole (SMBH) systems, and also show that the rates of these repeated ...events are high enough to be detected by the Large Synoptic Survey Telescope (LSST) over its lifetime. Therefore, these multiple TD events provide a novel method for identifying SMBH binary systems with parsec to subparsec separations. The rates of TDs are investigated using simulations of non-interacting stars initially orbiting a primary SMBH and the potential of the model stellar cusp. The stars are then evolved forward in time and perturbed by a secondary SMBH inspiraling from the edge of the cusp to its stalling radius. We find with conservative magnitude estimates that the next-generation transient survey LSST should detect multiple TDs in approximately three galaxies over five years of observation, though less conservative estimates could increase this rate by an order of magnitude.
Background/Aims: No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (M
r>1200) through the intestinal mucosa in man. The present study aimed ...to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse and mild to more advanced stages of liver disease, and to measure the concentration of endotoxins in the plasma, as these compounds derive from the intestinal flora and are suspected to contribute to the development of alcoholic liver disease (ALD).
Methods: The permeability to polyethylene glycol M
r 400, M
r 1500, M
r 4000, and M
r 10 000 and endotoxin plasma concentrations were measured in 54 patients with alcoholic liver disease, 19 of them with cirrhosis, and in 30 non-alcoholic healthy controls.
Results: Permeability to polyethylene glycol M
r 400 was found to be unchanged in patients with ALD in comparison to healthy controls, whereas polyethylene glycol M
r 1500 and M
r 4000 were recovered in about twice as high concentrations in the urine of ALD patients (
p<0.01). Polyethylene glycol M
r 10 000 was detected significantly less frequently in urine from healthy controls (0/30) than in urine of patients with alcoholic liver disease (20/54,
p<0.01). Endotoxin concentrations in the plasma of alcoholics were increased more than 5-fold compared to healthy controls (
p<0.01).
Conclusions: The results of this study indicate that alcohol abuse impairs the function of the intestinal barrier, which might enhance the translocation of bacterial toxins, thereby contributing to inflammatory processes in alcoholic liver disease.
Background
Infections are an important complication after stroke and negatively affect clinical outcome. While pneumonia and urinary tract infections are well recognized after stroke, the incidence ...and consequences of sepsis remain unclear. The aim of this study was to evaluate the frequency and characteristics of sepsis in patients undergoing endovascular therapy for large vessel occlusion stroke, and its association with clinical outcome.
Methods
We analyzed a cohort of patients who underwent endovascular therapy at a single center between 2016 and 2020. The diagnosis and timing of infections and Sequential Organ Failure Assessment scores were evaluated retrospectively to identify patients with sepsis. Patients with sepsis were compared to controls regarding clinical characteristics and outcome.
Results
Fifty-four of 406 patients (13.3%) were found to have sepsis. The median onset of sepsis was 2 days after admission. The majority of cases (85.2%) was caused by pneumonia. At 3 months, 72.5% of patients with sepsis were bedridden or dead compared to 25.7 and 42.7% of controls and patients with an infection without sepsis, respectively. The adjusted odds ratio (95% confidence interval) for a poor outcome was 5.4 (1.6–17.6) for patients with sepsis vs. controls, and 2.0 (0.8–5.2) for patients with sepsis vs. patients with an infection without sepsis.
Conclusions
Sepsis is a frequent complication after large vessel occlusion stroke, and may be associated with a poor clinical outcome. More studies are needed to determine specific risk factors and measures to early recognize and reduce the possibly negative impact of sepsis on outcome after stroke.
The interaction of aqueous nanoparticle dispersions, e.g. based on monoolein/poloxamer 407, with blood components is an important topic concerning especially the parenteral way of administration. ...Therefore, the influence of human and porcine plasma on dispersed cubic phases was investigated. Particle size measurements of mixtures with plasma indicated a decrease in particle size. In cryo-transmission electron micrographs, different structures could be found, which arose from the dispersed cubic phases under plasma contact. Non-cubic structures on the particle surface were decomposed first. Several phase transitions with the formation of smaller and sometimes larger particle fractions were observed beside remaining cubic structures. A very low but detectable hemolytic activity was found for the dispersed cubic phases based on monoolein and poloxamer 407, when compared to the hemolytic activity of cubic phases based on monoolein and poloxamer 188, on soy phosphatidylcholine, glycerol dioleate and polysorbate 80 or the parenteral fat emulsion Lipofundin MCT 20%.
Abstract This report is a summary of the symposium on Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences, organized by National Institute on Alcohol ...Abuse and Alcoholism, Office of Dietary Supplements, and National Institute of Diabetes and Digestive and Kidney Diseases of National Institutes of Health in Rockville, Maryland, October 11, 2006. Alcohol exposure can promote the growth of Gram-negative bacteria in the intestine, which may result in accumulation of endotoxin. In addition, alcohol metabolism by Gram-negative bacteria and intestinal epithelial cells can result in accumulation of acetaldehyde, which in turn can increase intestinal permeability to endotoxin by increasing tyrosine phosphorylation of tight junction and adherens junction proteins. Alcohol-induced generation of nitric oxide may also contribute to increased permeability to endotoxin by reacting with tubulin, which may cause damage to microtubule cytoskeleton and subsequent disruption of intestinal barrier function. Increased intestinal permeability can lead to increased transfer of endotoxin from the intestine to the liver and general circulation where endotoxin may trigger inflammatory changes in the liver and other organs. Alcohol may also increase intestinal permeability to peptidoglycan, which can initiate inflammatory response in liver and other organs. In addition, acute alcohol exposure may potentiate the effect of burn injury on intestinal bacterial growth and permeability. Decreasing the number of Gram-negative bacteria in the intestine can result in decreased production of endotoxin as well as acetaldehyde which is expected to decrease intestinal permeability to endotoxin. In addition, intestinal permeability may be preserved by administering epidermal growth factor, l -glutamine, oats supplementation, or zinc, thereby preventing the transfer of endotoxin to the general circulation. Thus reducing the number of intestinal Gram-negative bacteria and preserving intestinal permeability to endotoxin may attenuate alcoholic liver and other organ injuries.
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