In the present paper, we report results from a study of the structure and physicochemical properties of gold nanoparticles modified with poly(ethylene glycol) (PEG) designed for the drug delivery of ...the proteasome inhibitor Bortezomib (BTZ) in cancer therapy. A number of advanced analytical techniques were used to define important physicochemical characteristics such as composition, structure, surface properties, particle size and morphology. A new approach based on detailed NMR studies was employed to define specific intermolecular interactions and mechanisms of drug immobilization and location into surface modified gold nanoparticles (AuNPs). Particularly important information was gained from analysis of NMR spectroscopic parameters such as the spectral line shape, translation diffusion, the nuclear Overhauser effect (NOE) and spin-lattice relaxation (T1). The results confirmed the coexistence of two different types of BTZ inclusion into polyethylene glycol coated gold nanoparticles: (i) association with the polymer chains by weak H-bonds and/or dipole-charge interactions and (ii) adsorption on the surface of the gold nanoparticles. The results allowed for determination of the overall structure of Bortezomib loaded PEG coated AuNPs, which is related to the therapeutic drug efficacy and activity in the treatment of cancer.
In this study, vitamin B12, the most chemically complex and the largest molecule among all the vitamins, was successfully incorporated into zein microstructures via electrospinning and spray drying ...techniques. Scanning electron microscopy analysis revealed that different microstructures were obtained by electrospinning technique: films, microparticles and electrospun fibres. The vitamin B12 films presented a smooth surface and had around 90% of encapsulation efficiency. Vitamin B12-encapsulated zein microbeads, with a size of around 3 μm, were formed showing an efficiency of encapsulation of 91%. Electrospun fibres exhibited ribbon-shaped morphologies and had an encapsulation efficiency of 100%. By spray drying technique, wrinkled zein microparticles with vitamin B12 were produced with an encapsulation efficiency and product yield ranging between 71 and 95% and 67–83%, respectively.
Kinetic models were applied to the experimental release profiles. The Weibull kinetic model showed the best fitting with the experimental data. The main drug transport mechanism associated to the experimental data is the Fickian diffusion (case I transport).
The results suggest that the produced zein microstructures via spray drying and electrospinning techniques can be used as promising and effective alternative food and nutraceutical delivery systems.
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•Zein microstructures produced via spray drying and electrospinning techniques.•Microstructures are promising and effective food/nutraceutical delivery systems.•Electrospun fibres/microbeads and wrinkled microparticles with vitB12 were produced.•Microstructures with high encapsulation efficiency.•Weibull model is the best approach associated to B12 release kinetics.
The increased consumption of polymers and the consequent generation of waste requires the development of efficient recycling strategies. In this paper, poly(Ethylene–Vinyl Acetate) (EVA) waste with ...millimetric (1–3.15 mm) and micrometric (< 562 µm) granulometries were compared as lightweight aggregates substitutes for mortar. Additionally, millimetric EVA was coated with natural aggregates through a thermal treatment before mortar incorporation. The volumetric content of replaced natural aggregates in mortars ranged from 0 to 70%. It was concluded that the mortar density decreases with EVA incorporation, the stronger effect being obtained with millimetric EVA (22% vs 18%, for millimetric and micrometric EVA, 50% EVA). The flexural and compressive strengths decreased with increasing polymer replacement, although flexural strength was less affected than compressive strength and micrometric EVA proved to be less detrimental to the mechanical properties than millimetric EVA (50% vs 37% for flexural strength and 71% vs 64% for compressive strength for millimetric and micrometric EVA, 50% EVA). The water sorptivity coefficient substantially decreased with the addition of micrometric EVA. The less affected mechanical properties and better waterproofness achieved with the addition of micrometric EVA waste to mortar opens the possibility to obtain better quality polymer-substituted mortars with possible application in plasters or masonry laying.
In September 2012, a comprehensive survey of Pico Island was conducted along an elevational transect, starting at Manhenha (10 m a.s.l.) and culminating at the Pico Mountain caldera (2200 m a.s.l.). ...The primary objective was to systematically inventory the bryophytes inhabiting the best-preserved areas of native vegetation environments. Twelve sites were selected, each spaced at 200 m elevation intervals. Within each site, two 10 m x 10 m plots were established in close proximity (10-15 m apart). Within these plots, three 2 m x 2 m quadrats were randomly selected and sampled for bryophytes using microplots measuring 10 cm x 5 cm, which were then collected into paper bags. Six substrates were surveyed in each quadrat: rock, soil, humus, organic matter, tree bark and leaves/fronds. Three replicates were obtained from all substrates available and colonised by bryophytes, resulting in a maximum of 18 microplots per quadrat, 54 microplots per plot, 108 microplots per site, and a total of 1296 microplots across the 12 sites on Pico Island.
Two-thirds of the maximum expected number of microplots (n = 878; 67.75%) were successfully collected, yielding a total of 4896 specimens. The vast majority (n = 4869) were identified at the species/subspecies level. The study identified a total of 70 moss and 71 liverwort species or subspecies. Elevation levels between 600-1000 m a.s.l., particularly in the native forest plots, exhibited both a higher number of microplots and greater species richness. This research significantly enhanced our understanding of Azorean bryophyte diversity and distribution, contributing valuable insights at both local and regional scales. Notably, two new taxa for the Azores were documented during the MOVECLIM study, namely the pleurocarpous mosses
and
.
We investigated age-related changes in learning and memory performance and behavioural extinction in the water maze; and in endogenous levels of serotonin (5-HT) and 5-hydroxyindole acetic acid ...(5-HIAA) in the neocortex, hippocampus, thalamus and dorsal raphe nucleus of Wistar rats. Another aim was to assess the correlation between behavioural and biochemical parameters, which were measured in rodents of two different ages: 5 months (adults) and 16 months (middle-aged). The middle-aged subjects succeeded in learning the behavioural task, albeit with significantly worse performance when compared to adult animals. Aging also had significant main effects on memory and extinction. An age-dependent decrease in 5-HIAA levels was observed in both hippocampus and dorsal raphe nucleus (DRN). The decrease in DRN 5-HIAA was paralleled by a decrease in 5-HIAA/5-HT ratio in this brain area, which was significantly correlated to the animals’ spatial memory performance and behavioural extinction. In addition, using middle-aged rats, a 2
×
2 factorial study was carried out to examine the effects of food restriction and chronic ethanol consumption on rat's performance in a spatial behavioural task and on central serotonergic parameters. None of these two treatments had a significant effect on the behavioural and biochemical parameters assessed, with the exception of extinction index, which was significantly affected by ethanol consumption. Long-term ethanol ameliorated the impairment in behavioural flexibility caused by aging. In conclusion, long-term ethanol consumption may have a role in protecting against age-related deficit in behavioural extinction. Moreover, the present results also indicate that DRN serotonergic system is involved in spatial memory and behavioural extinction.
Abstract
Background
Pheochromocytomas and paragangliomas (PPGLs) have the highest degree of heritability among endocrine tumors. Currently, ∼40% of PPGL individuals have a genetic germline pathogenic ...variant and exist at least 12 different genetic syndromes related to these tumors. Pathogenic variants in the Succinate Dehydrogenase Complex Subunit B (SDHB) gene account for about 10% of PPGL cases. Moreover, SDHB pathogenic variants are the most well-established risk factor to predict metastatic disease (40%-50% of cases). Germline SDHB large deletions are very rare worldwide, but SDHB exon 1 deletion has been reported in patients with PPGLs from Portugal and Spain. Indeed, a putative founder effect for SDHB exon 1 deletion was suggested in PPGL patients from Iberian Peninsula.
Aim
To investigate a putative founder effect for SDHB exon 1 deletion.
Methods
Eighteen unrelated Brazilian patients with germline heterozygous SDHB pathogenic variants were included. Additionally, two unrelated individuals with SDHB exon 1 complete deletion from Argentina were studied. SDHB pathogenic variants were investigated by automated SAGER sequencing, multiplex ligation-dependent probe amplification (SALSA MLPA Probemix P226 SDH) and/or high-throughput sequencing. Five SDHB flanking microsatellite markers at chromosome 1p (D1S2697, GATA29A05, D1S2826, D1S2644, and D1S199) were used to investigate if patients carrying this deletion have a common origin. Haplotypes were reconstructed using the PHASE algorithm (v. 2.1). A control group comprising 26 unrelated Brazilian individuals was also studied.
Results
Among 18 Brazilian patients with germline SDHB pathogenic variants, heterozygous SDHB exon 1 complete deletion was identified in 6 of them (33% of the cases). The remaining 12 patients presented intragenic SDHB pathogenic variants without hotspot location. All Brazilian index patients with SDHB exon 1 deletion presented with paraganglioma, located mostly in the abdomen (4 abdominal; one thoracic; two head and neck and one colonic). Median age was 31.5 years and metastatic disease occurred in 3 (50%) of them. Haplotype analysis showed that 4 apparently unrelated Brazilian patients (4 out of 6 cases, 67%) shared a common allele (SDHB-GATA29A05-D1S2826-D1S2644-D1S199 | SDHB-186-130-213-102), which was not seen in chromosomes without the SDHB exon 1 deletion (p= 0.01). The two cases from Argentina did not have this haplotype, suggesting that SDHB exon 1 deletion in Argentina have a different origin.
Conclusion
SDHB exon 1 complete deletion was the most frequent SDHB defect in our cohort. Our findings indicate a founder effect for SDHB exon 1 complete deletion in Brazilian patients with paraganglioma.
Support: Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6
Presentation: Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
Relatively little is known about the outcomes of multiple myeloma in Latin America, a world region where incorporation of novel agents is generally slow. In the current retrospective-prospective ...study, we aimed to describe the patterns of care and treatment results in five Latin American countries. Between April 2007 and October 2009, patients who had been diagnosed from January 2005 to December 2007 were registered at 23 institutions from Argentina, Brazil, Chile, Mexico, and Peru. We divided patients into two cohorts, according to transplantation eligibility, and analyzed them with regard to first-line treatment and overall survival (OS). We analyzed a total of 852 patients, 46.9 % of whom were female. The median follow-up was 62 months. Among transplantation-ineligible patients (
N
= 461), the mean age was 67.4 years, approximately one third of patients received a thalidomide-based treatment in the first line, and the median OS was 43.0 months. Transplantation-eligible patients (
N
= 391) had a mean age of 54.7 years and a median OS of 73.6 months. Autologous transplantation was performed in 58.6 % of the patients for whom this procedure was initially planned and in only 26.9 % of the overall patients. Our long-term results reflect the contemporary literature for patients with multiple myeloma treated with autologous transplantation and thalidomide-based regimens in clinical trials and observational studies. However, further efforts are needed to approve and incorporate novel agents in Latin American countries, as well as to increase access to transplantation, in order to achieve the expected improvements in patient outcomes.
Cutaneous and visceral leishmaniasis are amongst the most devastating infectious diseases of our time, affecting millions of people worldwide. The treatment of these serious diseases rely on a few ...chemotherapeutic agents, most of which are of parenteral use and induce severe side-effects. Furthermore, rates of treatment failure are high and have been linked to drug resistance in some areas. Here, we reviewed data on current chemotherapy practice in leishmaniasis. Drug resistance and mechanisms of resistance are described as well as the prospects for applying drug combinations for leishmaniasis chemotherapy. It is clear that efforts for discovering new drugs applicable to leishmaniasis chemotherapy are essential. The main aspects on the various steps of drug discovery in the field are discussed.
There is growing concern that modifications to the global environment such as ocean acidification and increased ultraviolet radiation may interact with anthropogenic pollutants to adversely affect ...the future marine environment. Despite this, little is known about the nature of the potential risks posed by such interactions. Here, we performed a multifactorial microcosm experiment to assess the impact of ocean acidification, ultraviolet B (UV‐B) radiation and oil hydrocarbon contamination on sediment chemistry, the microbial community (composition and function) and biochemical marker response of selected indicator species. We found that increased ocean acidification and oil contamination in the absence of UV‐B will significantly alter bacterial composition by, among other things, greatly reducing the relative abundance of Desulfobacterales, known to be important oil hydrocarbon degraders. Along with changes in bacterial composition, we identified concomitant shifts in the composition of oil hydrocarbons in the sediment and an increase in oxidative stress effects on our indicator species. Interestingly, our study identifies UV‐B as a critical component in the interaction between these factors, as its presence alleviates harmful effects caused by the combination of reduced pH and oil pollution. The model system used here shows that the interactive effect of reduced pH and oil contamination can adversely affect the structure and functioning of sediment benthic communities, with the potential to exacerbate the toxicity of oil hydrocarbons in marine ecosystems.
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