74 research outputs found
Mathematical model of blood and interstitial flow and lymph production in the liver.
We present a mathematical model of blood and interstitial flow in the liver. The liver is treated as a lattice of hexagonal \u2018classic\u2019 lobules, which are assumed to be long enough that end effects may be neglected and a
two-dimensional problem considered. Since sinusoids and lymphatic vessels are numerous and small compared to the lobule, we use a homogenized approach, describing the sinusoidal and interstitial spaces as porous media. We model plasma filtration from sinusoids to the interstitium, lymph uptake by lymphatic ducts, and lymph outflow from the liver
surface. Our results show that the effect of the liver surface only penetrates a depth of a few lobules\u2019 thickness into the tissue. Thus, we separately consider a single lobule lying sufficiently far from all external boundaries that we may regard it as being in an infinite lattice, and also a model of the region near the liver surface. The model predicts that slightly more lymph is produced by interstitial fluid flowing through the liver surface than that taken up by the lymphatic vessels in the liver and that the on-peritonealized region of the surface of the liver results in the total lymph production (uptake by lymphatics plus fluid crossing surface) being about 5 % more than if the entire surface were covered by the Glisson\u2013peritoneal membrane. Estimates of lymph outflow through the surface of the liver are in good agreement with experimental data. We also study the effect of non-physiological values of the controlling parameters, particularly focusing
on the conditions of portal hypertension and ascites. To our knowledge, this is the first attempt to model lymph production in the liver. The model provides clinically relevant information about lymph outflow pathways and predicts the systemic response to pathological variations
The Abdominal Circulatory Pump
Blood in the splanchnic vasculature can be transferred to the extremities. We quantified such blood shifts in normal subjects by measuring trunk volume by optoelectronic plethysmography, simultaneously with changes in body volume by whole body plethysmography during contractions of the diaphragm and abdominal muscles. Trunk volume changes with blood shifts, but body volume does not so that the blood volume shifted between trunk and extremities (Vbs) is the difference between changes in trunk and body volume. This is so because both trunk and body volume change identically with breathing and gas expansion or compression. During tidal breathing Vbs was 50–75 ml with an ejection fraction of 4–6% and an output of 750–1500 ml/min. Step increases in abdominal pressure resulted in rapid emptying presumably from the liver with a time constant of 0.61±0.1SE sec. followed by slower flow from non-hepatic viscera. The filling time constant was 0.57±0.09SE sec. Splanchnic emptying shifted up to 650 ml blood. With emptying, the increased hepatic vein flow increases the blood pressure at its entry into the inferior vena cava (IVC) and abolishes the pressure gradient producing flow between the femoral vein and the IVC inducing blood pooling in the legs. The findings are important for exercise because the larger the Vbs the greater the perfusion of locomotor muscles. During asystolic cardiac arrest we calculate that appropriate timing of abdominal compression could produce an output of 6 L/min. so that the abdominal circulatory pump might act as an auxiliary heart
Physiological aspects of the determination of comprehensive arterial inflows in the lower abdomen assessed by Doppler ultrasound
Non-invasive measurement of splanchnic hemodynamics has been utilized in the clinical setting for diagnosis of gastro-intestinal disease, and for determining reserve blood flow (BF) distribution. However, previous studies that measured BF in a "single vessel with small size volume", such as the superior mesenteric and coeliac arteries, were concerned solely with the target organ in the gastrointestinal area, and therefore evaluation of alterations in these single arterial BFs under various states was sometimes limited to "small blood volumes", even though there was a relatively large change in flow. BF in the lower abdomen (BFAb) is potentially a useful indicator of the influence of comprehensive BF redistribution in cardiovascular and hepato-gastrointestinal disease, in the postprandial period, and in relation to physical exercise. BFAb can be determined theoretically using Doppler ultrasound by subtracting BF in the bilateral proximal femoral arteries (FAs) from BF in the upper abdominal aorta (Ao) above the coeliac trunk. Prior to acceptance of this method of determining a true BFAb value, it is necessary to obtain validated normal physiological data that represent the hemodynamic relationship between the three arteries. In determining BFAb, relative reliability was acceptably high (range in intra-class correlation coefficient: 0.85-0.97) for three arterial hemodynamic parameters (blood velocity, vessel diameter, and BF) in three repeated measurements obtained over three different days. Bland-Altman analysis of the three repeated measurements revealed that day-to-day physiological variation (potentially including measurement error) was within the acceptable minimum range (95% of confidence interval), calculated as the difference in hemodynamics between two measurements. Mean BF (ml/min) was 2951 ± 767 in Ao, 316 ± 97 in left FA, 313 ± 83 in right FA, and 2323 ± 703 in BFAb, which is in agreement with a previous study that measured the sum of BF in the major part of the coeliac, mesenteric, and renal arteries. This review presents the methodological concept that underlies BFAb, and aspects of its day-to-day relative reliability in terms of the hemodynamics of the three target arteries, relationship with body surface area, respiratory effects, and potential clinical usefulness and application, in relation to data previously reported in original dedicated research
Effects of salinity and drought on growth, ionic relations, compatible solutes and activation of antioxidant systems in oleander (Nerium oleander L.)
[EN] Nerium
oleander
is an
ornamental
species
of high
aesthetic
value,
grown
in arid
and
semi-
arid
regions
because
of its
drought
tolerance,
which
is also
considered
as
relatively
resistant
to salt;
yet
the
biochemical
and
molecular
mechanisms
underlying
oleander¿s
stress
toler-
ance
remain
largely
unknown.
To
investigate
these
mechanisms,
one-year-old
oleander
seedlings
were
exposed
to 15
and
30
days
of treatment
with
increasing
salt
concentratio
ns,
up
to 800
mM
NaCl,
and
to complete
withholding
of irrigation;
growth
parameters
and
bio-
chemical
markers
characteristic
of conserved
stress-response
pathways
were
then
deter-
mined
in stressed
and
control
plants.
Strong
water
deficit
and
salt
stress
both
caused
inhibition
of growth,
degradation
of photosynthetic
pigments,
a slight
(but
statistically
signifi-
cant)
increase
in the
leaf
levels
of specific
osmolytes,
and
induction
of oxidative
stress¿as
indicated
by
the
accumulation
of malondialdehyde
(MDA),
a reliable
oxidative
stress
marker
¿accompanied
by
increases
in the
levels
of total
phenolic
compounds
and
antioxidant
fla-
vonoids
and
in the
specific
activities
of ascorbate
peroxidase
(APX)
and
glutathione
reduc-
tase
(GR).
High
salinity,
in addition,
induced
accumulation
of Na
+
and
Cl
-
in roots
and
leaves
and
the
activation
of superoxide
dismutase
(SOD)
and
catalase
(CAT)
activities.
Apart
from
anatomical
adaptations
that
protect
oleander
from
leaf
dehydration
at moderate
levels
of
stress,
our
results
indicate
that
tolerance
of this
species
to salinity
and
water
deficit
is based
on
the
constitutive
accumulation
in leaves
of high
concentratio
ns
of soluble
carbohydrates
and,
to a lesser
extent,
of glycine
betaine,
and
in the
activation
of the
aforementioned
antiox-
idant
systems.
Moreover,
regarding
specifically
salt
stress,
mechanisms
efficiently
blocking
transport
of toxic
ions
from
the
roots
to the
aerial
parts
of the
plant
appear
to contribute
to a
large
extent
to tolerance
in
Nerium
oleanderThis work was financed by internal funds of the Polytechnic University of Valencia to Monica Boscaiu and Oscar Vicente. Dinesh Kumar’s stay in Valencia was financed by a NAMASTE fellowship from the European Union, and Mohamad Al Hassan was a recipient of an Erasmus Mundus pre-doctoral scholarship financed by the European Commission (Welcome Consortium).Kumar, D.; Al Hassan, M.; Naranjo Olivero, MA.; Agrawal, V.; Boscaiu, M.; Vicente, O. (2017). Effects of salinity and drought on growth, ionic relations, compatible solutes and activation of antioxidant systems in oleander (Nerium oleander L.). PLoS ONE. 12(9). doi:10.1371/journal.pone.0185017Se018501712
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
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