515 research outputs found
Pyrrolizidine alkaloids enhance alcohol-induced hepatocytotoxicity in vitro in normal human hepatocytes
OBJECTIVE : Herbal remedies containing
pyrrilidozine alkaloids (PA)s can induce liver
damage, including hepato-sinusoidal obstruction
syndrome (HSOS) or veno-occlusive liver disease
(VOD). Some individuals misusing alcohol consume
also teas and/or herbal remedies containing
PA. The interaction or additive toxicity of alcohol to
PA toxicity needs to be addressed. The objectives
of this study are 1) to review the scientific literature
on the PA-induced liver toxicity; 2) identify possible
mechanism(s) involved in PA-induced hepatocytotoxicity
in the presence or absence of ethanol
(EtOH) in vitro in normal human hepatocytes (NHH)
in primary culture. To respond to the first objective,
we systematically search all the literature engines
(PubMed, Google Scholar) for liver induced damage
due to PAs and summarize the results in an introductory
systematic review.
ORIGINAL ARTICLE EXPERIMENTAL DESIGN
AND METHODS : Cells were exposed to one
dose of 100 mmol/L EtOH for 24 hrs and to 2 doses
of 100 mmol/L EtOH for consecutive 24 hrs
periods, in the presence or absence of PAs (10
mg/mL), or the caspase-3 inhibitor IDN-1965 (50
μmol/L). Cells were analyzed for apoptosis by
light microscopy, immuno-histochemistry, measuring
cytokeratin-18 fragmentation, and transmission
electron microscopy (TEM) (6000 cells/
treatment). Cytotoxicity was determined using succinate dehydrogenase (SDH) activity, an enzyme
specific to the mitochondria.
RESULTS : In NHH cells, a 100 mmol/L dose of
Et-OH resulted in 22±2.5 apoptosis (p<0.001 vs.
control). Two consecutive doses of 100 mmol/L
Et-OH for 24 hrs each caused 36±3.0% apoptosis
(p<0.001 vs. control and p<0.05 vs. one dose Et-
OH). Pre-treatment with 50 μmol/L caspase inhibitor
significantly reduced Et-OH-induced apoptosis
[12±1.5% in 100 mmol/L (p<0.05) and 20±4.0%
in 2×100 mmol/L (p<0.001)]. In addition, pre-treatment
with 50 μmol caspase inhibitor in cells treated
with PA + EtOH reduced apoptosis significantly
(vs. non-exposed to caspase-inhibitor): Δ -22±3.0 % (p<0.05). HPC significantly decreased apoptosis
compared to conditions lacking this supplementation
in cells treated with EtOH-exposed
cells present ballooning, Mallory bodies, changes
in mitochondrial cristae and apoptosis by TEM.
Pre-treatment with 50 μmol caspase inhibitor significantly
reduced 100 mmol/L EtOH-induced (one
dose) in NHH by 14±0.5% (p<0.05) compared to
cells not exposed to the caspase-inhibitor. In cells
treated concomitantly with PA and EtOH 100 mM
Mallory-bodies and apo-necrotic cells have been
observed. Pre-treatment with 50 μmol caspase inhibitor
reduced the mitochondrial damage. A significant
depletion in glutathione (GSH) was observed
in Et-OH treated cells after 1 and 2 treatments
(p<0.001 vs. control). Treatment with E t-OH enhanced
PA-induced GSH-depletion and resulted
in a significant increase in PA-induced cytotoxicity
(p<0.001 vs. Et-untreated cells). Exposure to EtOH
increased the cell culture media levels of the pro-inflammatory
cytokine TNF. PA + EtOH-treated cells
increased TNF-α levels in media compared to EtOH
alone [86±8 vs. 53±5 pg/mL in cells exposed to 100
mmol/L EtOH (p<0.05) and 218±14 vs. 179±8 pg/mL
in cells exposed to 2×100 mmol/L EtOH (p<0.05)].
CONCLUSIONS : PA up-regulates EtOH-induced
hepatocytotoxicity by inducing the inflammatory
cytokines and enhancing the apoptotic effects
of ethanol. There is a need for monitoring herbal medicine in order to optimize traditional medicine
use and maximize the clinical benefits. Additionally,
there is necessary to communicate to physicians
the possible negative results of herbal remedies
use. Also, the interactions between herbal
remedies and drugs of misuse should be communicated
to consumers.The
work was funded by In Vitro Drug Safety and Biotechnology.
We are thankful for the financial contribution to Mahaffy
-Gastroenterology Fund, Sunnybrook HSC, Toronto,
ON, Canada.http://www.europeanreview.orgam2017Pharmacolog
Singularities in the Fermi liquid description of a partially filled Landau level and the energy gaps of fractional quantum Hall states
We consider a two dimensional electron system in an external magnetic field
at and near an even denominator Landau level filling fraction. Using a
fermionic Chern--Simons approach we study the description of the system's low
energy excitations within an extension of Landau's Fermi liquid theory. We
calculate perturbatively the effective mass and the quasi--particle interaction
function characterizing this description. We find that at an even denominator
filling fraction the fermion's effective mass diverges logarithmically at the
Fermi level, and argue that this divergence allows for an {\it exact}
calculation of the energy gaps of the fractional quantized Hall states
asymptotically approaching these filling fractions. We find that the
quasi--particle interaction function approaches a delta function. This singular
behavior leads to a cancelation of the diverging effective mass from the long
wavelength low frequency linear response functions at even denominator filling
fractions.Comment: 46 pages, RevTeX, 5 figures included in a uuencoded postscript file.
Minor revisions relative to the original version. The paper will be published
in the Physical Review B, and can be retrieved from the World Wide Web, in
http://cmtw.harvard.edu/~ster
A longitudinal investigation of repressive coping and ageing
This is an Accepted Manuscript of an article published by Taylor & Francis in Aging & Mental Health on October 2016, available online: http://www.tandfonline.com/doi/full/10.1080/13607863.2015.1060941.Two studies investigated the possibility that repressive coping is more prevalent in older adults and that this represents a developmental progression rather than a cohort effect. Study 1 examined repressive coping and mental health cross-sectionally in young and old adults. Study 2 examined whether there was a developmental progression of repressive coping prevalence rates in a longitudinal sample of older adults.Peer reviewedFinal Accepted Versio
Effect of a two-year national quality improvement program on surgical checklist implementation
Use of the surgical checklist in Switzerland is still incomplete and unsatisfactory. A national improvement program was developed and conducted in Switzerland to implement and improve the use of the surgical safety checklists. The aims of the implementation program were to implement comprehensive and correct checklist use in participating hospitals in every patient and in every surgical procedure; and to improve safety climate and teamwork as important cultural context variables. 10 hospitals were selected for participation in the implementation program. A questionnaire assessing use, knowledge, and attitudes towards the checklist and the Safety Climate Survey were conducted at two measurement occasions each in October/November 2013 and January/February 2015. Significant increases emerged for frequency of checklist use (F(1,1001)=340.9, p<0.001), satisfaction (F(1,1232)=25.6, p<0.001), and knowledge(F(1,1294)=184.5, p<0.001). While significant differences in norms (F(1,1284)=17.9, p<0.001) and intentions (F(1,1284)=7.8, p<0.01) were observed, this was not the case for attitudes (F(1,1283)=.8, n.s.) and acceptance (F(1,1284)=0.1, n.s.). Significant differences for safety climate and teamwork emerged in the present study (F(1,3555)=11.8, p<0.001 and F(1,3554)=24.6, p<0.001, respectively). However, although statistical significance was reached, effects are very small and practical relevance is thus questionable. The results of the present study suggest that the quality improvement program conducted by the Swiss Patient Safety Foundation in 10 hospitals led to successful checklist implementation. The strongest effects were seen in aspects concerning behaviour and knowledge specifically related to checklist use. Less impact was achieved on general cultural variables safety climate and teamwork. However, as a trend was observable, these variables may simply need more time in order to change substantially
A tetragonal-to-monoclinic phase transition in a ferroelectric perovskite: the structure of PbZr(0.52)Ti(0.48)O3
The perovskite-like ferroelectric system PbZr(1-x)Ti(x)O3 (PZT) has a nearly
vertical morphotropic phase boundary (MPB) around x=0.45-0.50. Recent
synchrotron x-ray powder diffraction measurements by Noheda et al. [Appl. Phys.
Lett. 74, 2059 (1999)] have revealed a new monoclinic phase between the
previously-established tetragonal and rhombohedral regions. In the present work
we describe a Rietveld analysis of the detailed structure of the tetragonal and
monoclinic PZT phases on a sample with x= 0.48 for which the lattice parameters
are respectively: at= 4.044 A, ct= 4.138 A, at 325 K, and am= 5.721 A, bm=
5.708 A, cm= 4.138 A, beta= 90.496 deg., at 20K. In the tetragonal phase the
shifts of the atoms along the polar [001] direction are similar to those in
PbTiO3 but the refinement indicates that there are, in addition, local
disordered shifts of the Pb atoms of ~0.2 A perpendicular to the polar axis..
The monoclinic structure can be viewed as a condensation along one of the
directions of the local displacements present in the tetragonal phase. It
equally well corresponds to a freezing-out of the local displacements along one
of the directions recently reported by Corker et al.[J. Phys. Condens.
Matter 10, 6251 (1998)] for rhombohedral PZT. The monoclinic structure
therefore provides a microscopic picture of the MPB region in which one of the
"locally" monoclinic phases in the "average" rhombohedral or tetragonal
structures freezes out, and thus represents a bridge between these two phases.Comment: REVTeX, 7 figures. Modifications after referee's suggestion: new
figure (figure 5), comments in 2nd para. (Sect.III) and in 2nd & 3rd para.
(Sect. IV-a), in the abstract: "...of ~0.2 A perpendicular to the polar
axis.
On twisted Fourier analysis and convergence of Fourier series on discrete groups
We study norm convergence and summability of Fourier series in the setting of
reduced twisted group -algebras of discrete groups. For amenable groups,
F{\o}lner nets give the key to Fej\'er summation. We show that Abel-Poisson
summation holds for a large class of groups, including e.g. all Coxeter groups
and all Gromov hyperbolic groups. As a tool in our presentation, we introduce
notions of polynomial and subexponential H-growth for countable groups w.r.t.
proper scale functions, usually chosen as length functions. These coincide with
the classical notions of growth in the case of amenable groups.Comment: 35 pages; abridged, revised and update
Lorentz breaking Effective Field Theory and observational tests
Analogue models of gravity have provided an experimentally realizable test
field for our ideas on quantum field theory in curved spacetimes but they have
also inspired the investigation of possible departures from exact Lorentz
invariance at microscopic scales. In this role they have joined, and sometime
anticipated, several quantum gravity models characterized by Lorentz breaking
phenomenology. A crucial difference between these speculations and other ones
associated to quantum gravity scenarios, is the possibility to carry out
observational and experimental tests which have nowadays led to a broad range
of constraints on departures from Lorentz invariance. We shall review here the
effective field theory approach to Lorentz breaking in the matter sector,
present the constraints provided by the available observations and finally
discuss the implications of the persisting uncertainty on the composition of
the ultra high energy cosmic rays for the constraints on the higher order,
analogue gravity inspired, Lorentz violations.Comment: 47 pages, 4 figures. Lecture Notes for the IX SIGRAV School on
"Analogue Gravity", Como (Italy), May 2011. V.3. Typo corrected, references
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Avaliação do processo de atendimento a pacientes portadores de doença crônico-degenerativa em uma unidade básica de saúde
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