728 research outputs found
Myrtucommulone from Myrtus communis exhibits potent anti-inflammatory effectiveness in vivo.
Myrtucommulone a nonprenylated acylphloroglucinol contained in the leaves of myrtle (Myrtus communis), has been reported to suppress the biosynthesis of eicosanoids by inhibition of 5-lipoxygenase and cyclooxygenase-1 in vitro and to inhibit the release of elastase and the formation of reactive oxygen species in activated polymorphonuclear leukocytes. Here, in view of the ability of MC to suppress typical proinflammatory cellular responses in vitro, we have investigated the effects of MC in in vivo models of inflammation. MC was administered to mice intraperitoneally, and paw edema and pleurisy were induced by the subplantar and intrapleural injection of carrageenan, respectively. MC (0.5, 1.5, and 4.5 mg/kg i.p.) reduced the development of mouse carrageenan-induced paw edema in a dose-dependent manner. Moreover, MC (4.5 mg/kg i.p. 30 min before and after carrageenan) exerted anti-inflammatory effects in the pleurisy model. In particular, 4 h after carrageenan injection in the pleurisy model, MC reduced: 1) the exudate volume and leukocyte numbers; 2) lung injury (histological analysis) and neutrophil infiltration (myeloperoxidase activity); 3) the lung intercellular adhesion molecule-1 and P-selectin immunohistochemical localization; 4) the cytokine levels (tumor necrosis factor-α and interleukin-1 β in the pleural exudate and their immunohistochemical localization in the lung; 5) the leukotriene B 4, but not prostaglandin E2, levels in the pleural exudates; and 6) lung peroxidation (thiobarbituric acid-reactant substance) and nitrotyrosine and poly (ADP-ribose) immunostaining. In conclusion, our results demonstrate that MC exerts potent anti-inflammatory effects in vivo and offer a novel therapeutic approach for the management of acute inflammation. Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics
Parabolic oblique derivative problem in generalized Morrey spaces
We study the regularity of the solutions of the oblique derivative problem
for linear uniformly parabolic equations with VMO coefficients. We show that if
the right-hand side of the parabolic equation belongs to certain generalized
Morrey space than the strong solution belongs to the corresponding generalized
Sobolev-Morrey space
Dynamical response of the Galileo Galilei on the ground rotor to test the equivalence principle: Theory, simulation, and experiment. II. The rejection of common mode forces
"Galileo Galilei on the ground" (GGG) is a fast rotating differential accelerometer designed to test the equivalence principle (EP). Its sensitivity to differential effects, such as the effect of an EP violation, depends crucially on the capability of the accelerometer to reject all effects acting in common mode. By applying the theoretical and simulation methods reported in Part I of this work, and tested therein against experimental data, we predict the occurrence of an enhanced common mode rejection of the GGG accelerometer. We demonstrate that the best rejection of common mode disturbances can be tuned in a controlled way by varying the spin frequency of the GGG rotor. (c) 2006 American Institute of Physics
Dynamical response of the "GGG" rotor to test the Equivalence Principle: theory, simulation and experiment. Part I: the normal modes
Recent theoretical work suggests that violation of the Equivalence Principle
might be revealed in a measurement of the fractional differential acceleration
between two test bodies -of different composition, falling in the
gravitational field of a source mass- if the measurement is made to the level
of or better. This being within the reach of ground based
experiments, gives them a new impetus. However, while slowly rotating torsion
balances in ground laboratories are close to reaching this level, only an
experiment performed in low orbit around the Earth is likely to provide a much
better accuracy.
We report on the progress made with the "Galileo Galilei on the Ground" (GGG)
experiment, which aims to compete with torsion balances using an instrument
design also capable of being converted into a much higher sensitivity space
test.
In the present and following paper (Part I and Part II), we demonstrate that
the dynamical response of the GGG differential accelerometer set into
supercritical rotation -in particular its normal modes (Part I) and rejection
of common mode effects (Part II)- can be predicted by means of a simple but
effective model that embodies all the relevant physics. Analytical solutions
are obtained under special limits, which provide the theoretical understanding.
A simulation environment is set up, obtaining quantitative agreement with the
available experimental data on the frequencies of the normal modes, and on the
whirling behavior. This is a needed and reliable tool for controlling and
separating perturbative effects from the expected signal, as well as for
planning the optimization of the apparatus.Comment: Accepted for publication by "Review of Scientific Instruments" on Jan
16, 2006. 16 2-column pages, 9 figure
A kinetic study of gamma-glutamyltransferase (GGT)-mediated S-nitrosoglutathione catabolism.
S-Nitrosoglutathione (GSNO) is a nitric oxide (NO) donor compound which has been postulated to be
involved in transport of NO in vivo. It is known that c-glutamyl transpeptidase (GGT) is one of the
enzymes involved in the enzyme-mediated decomposition of GSNO, but no kinetics studies of the reaction
GSNO-GGT are reported in literature.
In this study we directly investigated the kinetics of GGT with respect to GSNO as a substrate and glycyl-
glycine (GG) as acceptor co-substrate by spectrophotometry at 334 nm. GGT hydrolyses the c-glutamyl
moiety of GSNO to give S-nitroso-cysteinylglycine (CGNO) and c-glutamyl-GG. However, as both
the substrate GSNO and the first product CGNO absorb at 334 nm, we optimized an ancillary reaction
coupled to the enzymatic reaction, based on the copper-mediated decomposition of CGNO yielding oxidized
cysteinyl-glycine and NO. The ancillary reaction allowed us to study directly the GSNO/GGT kinetics
by following the decrease of the characteristic absorbance of nitrosothiols at 334 nm. A Km of GGT for
GSNO of 0.398 ± 31 mM was thus found, comparable with Km values reported for other c-glutamyl substrates
of GGT
Effect of PD98059, a selective MAPK3/MAPK1 inhibitor, on acute lung injury in mice.
The aim of the present study is to evaluate the contribution of mitogen-activated protein kinase 1–3 (MAPK3/MAPK1) in a model of acute lung inflammation in mice. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent adhesion molecule expression (I-CAM and P-selectin), lipid peroxidation, and increased production of tumour necrosis factor-α, (TNF-α) and interleukin-1β (IL-1β). Furthermore, carrageenan induced lung apoptosis (Bax and Bcl-2 expression) as well as nitrotyrosine formation, NF-κB activation, and pJNK expression, as determined by immunohistochemical analysis of lung tissues and the degree of lung inflammation and tissue injury (histological score). Administration of PD98059, an inhibitor of MAPK3/MAPK1 (10 mg/kg) 1 h after carrageenan caused a reduction in all the parameters of inflammation measured. Thus, based on these findings we propose that inhibitors of the MAPK3/MAPK1 signaling pathways, such as PD98059, may be useful in the treatment of various inflammatory diseases
Recovery of a Medieval Brucella melitensis genome using shotgun metagenomics
ABSTRACT Shotgun metagenomics provides a powerful assumption-free approach to the recovery of pathogen genomes from contemporary and historical material. We sequenced the metagenome of a calcified nodule from the skeleton of a 14th-century middle-aged male excavated from the medieval Sardinian settlement of Geridu. We obtained 6.5-fold coverage of a Brucella melitensis genome. Sequence reads from this genome showed signatures typical of ancient or aged DNA. Despite the relatively low coverage, we were able to use information from single-nucleotide polymorphisms to place the medieval pathogen genome within a clade of B. melitensis strains that included the well-studied Ether strain and two other recent Italian isolates. We confirmed this placement using information from deletions and IS711 insertions. We conclude that metagenomics stands ready to document past and present infections, shedding light on the emergence, evolution, and spread of microbial pathogens
Human ectoparasites and the spread of plague in Europe during the Second Pandemic
Plague, caused by the bacterium Yersinia pestis, can spread through human populations by multiple transmission pathways. Today, most human plague cases are bubonic, caused by spillover of infected fleas from rodent epizootics, or pneumonic, caused by inhalation of infectious droplets. However, little is known about the historical spread of plague in Europe during the Second Pandemic (14-19th centuries), including the Black Death, which led to high mortality and recurrent epidemics for hundreds of years. Several studies have suggested that human ectoparasite vectors, such as human fleas (Pulex irritans) or body lice (Pediculus humanus humanus), caused the rapidly spreading epidemics. Here, we describe a compartmental model for plague transmission by a human ectoparasite vector. Using Bayesian inference, we found that this model fits mortality curves from nine outbreaks in Europe better than models for pneumonic or rodent transmission. Our results support that human ectoparasites were primary vectors for plague during the Second Pandemic, including the Black Death (1346-1353), ultimately challenging the assumption that plague in Europe was predominantly spread by rats
The recovery of octocoral populations following periodic disturbance masks their vulnerability to persistent global change
Funding: This research was funded by the US National Science Foundation through a series of grants to PJE (OCE 13-32915 and OCE 17-56678) and HRL (OCE 13-34052, OCE 17-56381 and OCE 18-01475) and was carried out under the necessary permits from the National Park Service (most recently VIIS-2019-SCI-0022).As the major form of coral reef regime shift, stony coral to macroalgal transitions have received considerable attention. In the Caribbean, however, regime shifts in which scleractinian corals are replaced by octocoral assemblages hold potential for maintaining reef associated communities. Accordingly, forecasting the resilience of octocoral assemblages to future disturbance regimes is necessary to understand these assemblages’ capacity to maintain reef biodiversity. We parameterised integral projection models quantifying the survival, growth, and recruitment of the octocorals, Antillogorgia americana, Gorgonia ventalina, and Eunicea flexuosa, in St John, US Virgin Islands, before, during, and after severe hurricane disturbance. Using these models, we forecast the density of populations of each species under varying future hurricane regimes. We demonstrate that although hurricanes reduce population growth, A. americana, G. ventalina, and E. flexuosa each display a capacity for quick recovery following storm disturbance. Despite this recovery potential, we illustrate how the population dynamics of each species correspond with a longer- term decline in their population densities. Despite their resilience to periodic physical disturbance events, ongoing global change jeopardises the future viability of octocoral assemblages.Peer reviewe
Demographic parameters of two populations of red coral (Corallium rubrum L. 1758) in the North Western Mediterranean
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