58 research outputs found
Proteoglycans, glycosaminoglycans and sulfated polysaccharides from connective tissues
Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium
The antimalarial activity of heparin, against which there are no
resistances known, has not been therapeutically exploited due to
its potent anticoagulating activity. Here, we have explored the
antiplasmodial capacity of heparin-like sulfated polysaccharides
from the sea cucumbers Ludwigothurea grisea and Isostichopus
badionotus, from the red alga Botryocladia occidentalis, and
from the marine sponge Desmapsamma anchorata. In vitro
experiments demonstrated for most compounds significant
inhibition of Plasmodium falciparum growth at low-anticoagulant
concentrations. This activity was found to operate through
inhibition of erythrocyte invasion by Plasmodium, likely
mediated by a coating of the parasite similar to that observed
for heparin. In vivo four-day suppressive tests showed that
several of the sulfated polysaccharides improved the survival of
Plasmodium yoelii-infected mice. In one animal treated with I.
badionotus fucan parasitemia was reduced from 10.4% to
undetectable levels, and Western blot analysis revealed the
presence of antibodies against P. yoelii antigens in its plasma.
The retarded invasion mediated by sulfated polysaccharides, and
the ensuing prolonged exposure of Plasmodium to the immune
system, can be explored for the design of new therapeutic
approaches against malaria where heparin-related polysaccharides
of low anticoagulating activity could play a dual role as drugs
and as potentiators of immune responses
Estudos preliminares com o predador Zelus sp. (Heteroptera: reduviidae) alimentado com lagartas de Spodoptera frugiperda (Lepidoptera: noctuidae) ou Tenebrio molitor (Coleoptera: Tenebrionidae).
Adhesion of freshwater sponge cells mediated by carbohydrate-carbohydrate interactions requires low environmental calcium
Marine ancestors of freshwater sponges had to undergo a
series of physiological adaptations to colonize harsh and
heterogeneous limnic environments. Besides reduced salinity,
river-lake systems also have calcium concentrations far lower
than seawater. Cell adhesion in sponges is mediated by
calcium-dependent multivalent self-interactions of sulfated
polysaccharides components of membrane-bound proteoglycans named
aggregation factors. Cells of marine sponges require seawater
average calcium concentration (10\xC2\xA0mM) to sustain adhesion
promoted by aggregation factors. We demonstrate here that the
freshwater sponge Spongilla alba can thrive in a calcium-poor
aquatic environment and that their cells are able to aggregate
and form primmorphs with calcium concentrations 40-fold lower
than that required by marine sponges cells. We also find that
their gemmules need calcium and other micronutrients to hatch
and generate new sponges. The sulfated polysaccharide purified
from S. alba has sulfate content and molecular size notably
lower than those from marine sponges. Nuclear magnetic resonance
analyses indicated that it is composed of a central backbone of
non- and 2-sulfated \xCE\xB1- and \xCE\xB2-glucose units
decorated with branches of \xCE\xB1-glucose. Assessments with
atomic force microscopy/single-molecule force spectroscopy show
that S. alba glucan requires 10-fold less calcium than sulfated
polysaccharides from marine sponges to self-interact
efficiently. Such an ability to retain multi-cellular morphology
with low environmental calcium must have been a crucial
evolutionary step for freshwater sponges to successfully
colonize inland waters
Fucosylated Chondroitin Sulfate Inhibits Plasmodium Falciparum Cytoadhesion And Merozoite Invasion.
Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect to P. falciparum cytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.581862-7
Heparins Sourced From Bovine and Porcine Mucosa Gain Exclusive Monographs in the Brazilian Pharmacopeia
Most of the unfractionated heparin (UFH) consumed worldwide is manufactured using porcine mucosa as raw material (HPI); however, some countries also employ products sourced from bovine mucosa (HBI) as interchangeable versions of the gold standard HPI. Although accounted as a single UFH, HBI, and HPI have differing anticoagulant activities (~100 and 200 IU mg−1, respectively) because of their compositional dissimilarities. The concomitant use of HBI and HPI in Brazil had already provoked serious bleeding incidents, which led to the withdrawal of HBI products in 2009. In 2010, the Brazilian Pharmacopeia (BP) formed a special committee to develop two complementary monographs approaching HBI and HPI separately, as distinct active pharmaceutical ingredients (APIs). The committee has rapidly agreed on requirements concerning the composition and presence of contaminants based on nuclear magnetic resonance and anion-exchange chromatography. On the other hand, consensus on the anticoagulant activity of HBI was the subject of long and intense discussions. Nevertheless, the committee has ultimately agreed to recommend minimum anti-FIIa activities of 100 IU mg−1 for HBI and 180 IU mg−1 for HPI. Upon the approval by the Brazilian Health Authority (ANVISA), the BP published the new monographs for HPI and HBI APIs in 2016 and 2017, respectively. These pioneer monographs represent a pivotal step toward the safest use of HBI and HPI as interchangeable anticoagulants and serve as a valuable template for the reformulation of pharmacopeias of other countries willing to introduce HBI
Rising from the Sea: Correlations between Sulfated Polysaccharides and Salinity in Plants
High salinity soils inhibit crop production worldwide and represent a serious agricultural problem. To meet our ever-increasing demand for food, it is essential to understand and engineer salt-resistant crops. In this study, we evaluated the occurrence and function of sulfated polysaccharides in plants. Although ubiquitously present in marine algae, the presence of sulfated polysaccharides among the species tested was restricted to halophytes, suggesting a possible correlation with salt stress or resistance. To test this hypothesis, sulfated polysaccharides from plants artificially and naturally exposed to different salinities were analyzed. Our results revealed that the sulfated polysaccharide concentration, as well as the degree to which these compounds were sulfated in halophytic species, were positively correlated with salinity. We found that sulfated polysaccharides produced by Ruppia maritima Loisel disappeared when the plant was cultivated in the absence of salt. However, subjecting the glycophyte Oryza sativa Linnaeus to salt stress did not induce the biosynthesis of sulfated polysaccharides but increased the concentration of the carboxylated polysaccharides; this finding suggests that negatively charged cell wall polysaccharides might play a role in coping with salt stress. These data suggest that the presence of sulfated polysaccharides in plants is an adaptation to high salt environments, which may have been conserved during plant evolution from marine green algae. Our results address a practical biological concept; additionally, we suggest future strategies that may be beneficial when engineering salt-resistant crops
Moving in the anthropocene: global reductions in terrestrial mammalian movements
Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission
Divergent cerebrospinal fluid cytokine network induced by non-viral and different viral infections on the central nervous system
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