It has been proposed that Tourette syndrome is associated with dysfunction in widespread cortical areas and globus pallidus externus hyperactivity secondary to dopaminergic hyperactivity and ...serotonergic/dynorphinergic hypoactivity. The main objective of this study was to test this hypothesis by developing an animal model of Tourette syndrome via striatotomy, followed by administration of drugs that mimic the neurotransmitter environment, so as to induce globus pallidus externus hyperactivity.
Rats were assigned to 3 groups: stereotactic striatotomy (STT) and striatal sham -lesion (SHAM) groups, treated with anterior and posterior striatum procedures in both hemispheres, and a group of nonoperated animals (NAIVE). Postoperatively, all rodents were blindly administered 3 drug protocols: levodopa/benserazide; levodopa/benserazide/ergotamine/naloxone (MIX); and saline. The animals were filmed at the peak action of these drugs. The videos were evaluated by a single blinded researcher.
Six types of involuntary movements (IMs) were observed: cephalic, trunk jerks, oromandibular, forepaw jerks, dystonic, and locomotive. The number of animals with IM and the mean number of IM after both levodopa/benserazide and MIX was significantly higher in the STT compared with the SHAM and NAIVE groups. In the SHAM and NAIVE, MIX was superior to levodopa/benserazide in the induction of IM. In the STT, MIX was superior to levodopa/benserazide in the induction of trunk jerks. Appendicular IM were more common after posterior than after anterior striatotomy.
These results show that striatotomy, followed by administration of levodopa/benserazide alone or associated with ergotamine and naloxone, is efficacious in inducing IM, supporting the hypothesis that led to this study.
Raman spectroscopy, optical microscopy, scanning electron microscopy (SEM), and electron probe microanalysis (EPMA) were used to study pigments on an Egyptian cartonnage from the Ptolemaic period ...(305–30 bc). The surface morphology of each color region was examined using backscattering (BS) and secondary electron imaging. SEM X‐ray energy dispersive spectrometry and EPMA wavelength dispersive spectroscopy provided semiquantitative chemical analysis of each pigment. Raman spectroscopy was used to identify the minerals associated with the pigments. This technique confirmed the presence of cinnabar (α‐HgS) in the red part of the fragments. A mixture of orpiment (As2S3) and bonazziite (β‐As4S4) and/or alacránite (As8S9) was detected in the yellow regions of the fragments. The orange pigment was confirmed to be a mixture of orpiment, uzonite (χ‐As4S5), and pararealgar (As4S4). Egyptian blue (CaCuSi4O10) and Egyptian green ((Cu,Ca)SiO3) pigments were detected from blue/green dark‐colored regions of the fragments.
Abstract We recently demonstrated that immunization with polyester poly(lactide-co-glycolide acid) (PLGA) nanoparticles loaded with the 11-kDa Leishmania vaccine candidate kinetoplastid membrane ...protein 11 (KMP-11) significantly reduced parasite load in vivo. Presently, we explored the ability of the recombinant PLGA nanoparticles to stimulate innate responses in macrophages and the outcome of infection with Leishmania braziliensis in vitro. Incubation of macrophages with KMP-11-loaded PLGA nanoparticles significantly decreased parasite load. In parallel, we observed the augmented production of nitric oxide, superoxide, TNF-α and IL-6. An increased release of CCL2/MCP-1 and CXCL1/KC was also observed, resulting in macrophage and neutrophil recruitment in vitro. Lastly, the incubation of macrophages with KMP-11-loaded PLGA nanoparticles triggered the activation of caspase-1 and the secretion of IL-1β and IL-18, suggesting inflammasome participation. Inhibition of caspase-1 significantly increased the parasite load. We conclude that KMP-11-loaded PLGA nanoparticles promote the killing of intracellular Leishmania parasites through the induction of potent innate responses. From the Clinical Editor In this novel study, KMP-11-loaded PLGA nanoparticles are demonstrated to promote the killing of intracellular Leishmania parasites through enhanced innate immune responses by multiple mechanisms. Future clinical applications would have a major effect on our efforts to address parasitic infections.
Fresh produce have a more limited shelf life than processed ones. Their sensory attributes such as appearance and surface texture are important features in consumer perception and liking. The ...decomposition of fresh produce, which is caused by enzymes, chemical reactions, and microbial infections, often caused by Colletotrichum species, is inevitable. However, it can be slowed down. Several materials have been developed for this purpose, with an emphasis on active coatings using nanomaterials. In this study, the protective effects of a zein coating containing chitosan nanowhiskers (CSW) for the maintenance of fruit quality were investigated using guava (Psidium guajava L.) as a model fruit. CSW were previously characterized, and their antifungal effects against distinct Colletotrichum species (Colletotrichum asianum, Colletotrichum tropicale, Colletotrichum gloeosporioides, and Colletotrichum brevisporum) were proven. Coatings were characterized by thermogravimetric analysis, optical profilometry, and mechanical properties. Total soluble solids, pH, mass loss, and visual inspection of uncoated and coated guava fruits were also verified during 9 days. Results show that CSW length and aspect ratio decreased for longer extraction times. A similar behavior was found for x‐ray diffraction in which peak intensity decreases under the same conditions. CSW degradation (ca. 250–400°C) also depends on extraction time in which more crystalline whiskers are the most thermally stable ones. The addition of CSW did not significantly (p < 0.05) modify the homogeneity and continuity of coating but prevented microbial growth assuring fruit quality during storage. In summary, coatings protected guava fruits from post‐harvest spoilage while preserving quality and extending shelf life.
Practical Application
Fresh foods such as fruits and vegetables have a more limited shelf life than processed ones.
Vaccine development has been a priority in the fight against leishmaniases, which are vector-borne diseases caused by Leishmania protozoa. Among the different immunization strategies employed to date ...is inoculation of plasmid DNA coding for parasite antigens, which has a demonstrated ability to induce humoral and cellular immune responses. In this sense, inoculation of plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was able to confer protection against visceral leishmaniasis. However, recently the use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles has also proven effective for eliciting protective immune responses.
In the present work, we tested two immunization strategies with the goal of obtaining protection, in terms of lesion development and parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP-11. Alternatively, mice were primed with PLGA nanoparticles loaded with the recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with recombinant KMP-11.
Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti-inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development was not inhibited following either immunization strategy. However, immunization with PLGA nanoparticles resulted in a more prominent reduction in parasite load at the infection site when compared with immunization using plasmid DNA alone. This effect was associated with a local increase in interferon-gamma and in tumor necrosis factor-alpha. Both immunization strategies also resulted in a lower parasite load in the draining lymph nodes, albeit not significantly.
Our results encourage the pursuit of immunization strategies employing nanobased delivery systems for vaccine development against cutaneous leishmaniasis caused by L. braziliensis infection.
Highlights ► Four antigenic proteins are characterized in Leishmania major ribosome: S4, S6, L3 and L5. ► Immunization with LmL3 or LmL5 plus CpG-ODN induces antigen specific Th1-responses in mice. ► ...Vaccines based on LmL3 and LmL5 induce protection against L. major challenge in BALB/c mice. ► Vaccines based on LmL3 and LmL5 also induces protection against L. braziliensis challenge. ► Protection correlates to the adjuvant-mediated induction of Th1 responses.
We explored furin substrate requirements in addition to the motif R-X-K/R-R using synthetic fluorescent resonance energy transfer (FRET) decapeptides. These decapeptides were derived from furin ...cleavage sites in viral coat glycoproteins and human and bacterial protein precursors. The hydrolysis by furin of most substrate was activated by K
+ ion, whereas kosmotropic anions of the Hofmeister series were inhibitors. The analysis of furin hydrolytic activity showed that its efficiency is highly dependent on the particular combinations of amino acids at different substrate positions. There is a clear interdependence of furin subsites that must be taken in account in determining its specificity and also for the design of inhibitors. However, clear preferences were detected for substrates with S at P
1′, and V at P
2′, at P
3′ the amino acids D, S, L and A are almost equally frequent. In the non-prime subsites the best substrates presented S and H at P
6; basic amino acids at P
5; and no clear tendency at P
3. Interestingly, two amino acid substitutions on the prime side of the peptide derived from H5N1 influenza hemagglutinin furin processing site highly improved its hydrolysis. These modifications are possible by single point mutations, suggesting a potential yield of a more infectious virus.
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