•Biobetters are improved biological drugs, usually with better pharmacokinetics.•Biobetters can be considered in between biosimilars and innovative biological drugs.•Biobetters take about 10 years of ...development with investments of $500 millions.•Glycosylation and PEGylation are the most common strategies to develop biobetters.•Innovative trends of genetic engineering are promising for biobetters development.
Biological drugs or biopharmaceuticals off patent open a large market for biosimilars and biobetters, follow-on biologics. Biobetters, in particular, are new drugs designed from existing ones with improved properties such as higher selectivity, stability, half-life and/or lower toxicity/immunogenicity. Glycosylation is one of the most used strategies to improve biological drugs, nonetheless bioconjugation is an additional alternative and refers to the covalent attachment of polymers to biological drugs. Extensive research on novel polymers is underway, nonetheless PEGylation is still the best alternative with the longest clinical track record. Innovative trends based on genetic engineering techniques such as fusion proteins and PASylation are also promising. In this review, all these alternatives wereexplored as well as current market trends, legislation and future perspectives.
Despite technological advances in the production processes of the materials for ceramic façade coatings, the problems of detachments are still frequent. Therefore, this work aims to investigate, ...through a literature review, the existing gaps related to the adhesion ability of adhesive mortars, identifying new research needs that can better explain the behavior of the material. In addition, an experimental procedure was developed to evaluate the mechanical capacity of adhesive mortars when subjected to cyclic stresses. Dynamic stress measurements are presented for several blocks of mortar and on similar blocks but with a slot drilled prior to measurements (intended to represent failure). From these data we calculated values of stress energy, elastic energy, and dissipated energy. The experimental results showed that the energy involved in the test process accompanied the load values and current stress values. The mortar samples with the previous failure absorbed and dissipated less energy than mortars without failure, showing that materials that have less energy to dissipate, are materials that have developed less capacity to adhere, that is, to keep their parts together.
Blubber samples from three delphinid species (false killer whale, Guiana and rough-toothed dolphin), as well as liver samples from franciscana dolphins were analyzed for dioxins and related compounds ...(DRCs). Samples were collected from 35 cetaceans stranded or incidentally captured in a highly industrialized and urbanized area (Southeast and Southern Brazilian regions). Dioxin-like PCBs accounted for over 83% of the total TEQ for all cetaceans. Non-ortho coplanar PCBs, for franciscanas (82%), and mono-ortho PCBs (up to 80%), for delphinids, constituted the groups of highest contribution to total TEQ. Regarding franciscana dolphins, significant negative correlations were found between total length (TL) and three variables, ΣTEQ-DRCs, ΣTEQ-PCDF and ΣTEQ non-ortho PCB. An increasing efficiency of the detoxifying activity with the growth of the animal may be a plausible explanation for these findings. This hypothesis is reinforced by the significant negative correlation found between TL and PCB126/PCB169 concentration ratio. DRC concentrations (ng/glipids) varied from 36 to 3006, for franciscana dolphins, as well as from 356 to 30,776, for delphinids. The sum of dioxin-like and indicator PCBs varied from 34,662 to 279,407ng/glipids, for Guiana dolphins from Rio de Janeiro state, which are among the highest PCB concentrations ever reported for cetaceans. The high concentrations found in our study raise concern not only on the conservation of Brazilian coastal cetaceans, but also on the possibility of human health problem due to consumption of fish from Brazilian estuaries.
•Dioxin-like PCBs accounted for over 83% of the total TEQ for all cetaceans•Negative correlations were found between length and TEQ values in franciscanas.•PCB concentrations found are among the highest ever reported for cetaceans.
In several countries, flower import regulations are restricted to food security, by establishing maximum residue limits (MRL) for pesticides in flower-based food products and biosafety, in order to ...limit the circulation of vectors, pests and exotic species across borders. In this context, the lack of limits on pesticides in flower-products for ornamental purposes can influence the pesticide overuse in production areas, as well as the transfer of contaminated products between countries. Therefore, the purpose of this review was to discuss possible adverse effects on human and environmental health of pesticides used in floriculture, evaluating regulations on the use of these pesticides in the main importing and flower-producing countries. This review included 92 documents. The use of 201 compounds was identified by interviews and analytical measurements. Among them, 93 are banned by the European Union (EU), although 46.3 % of these compounds have been identified in samples from European countries. Latin American countries have a large number of scientific publications on pesticides in flower production (n = 51), while the EU and China have less studies (n = 24) and the United States and Japan have no studies. Regarding adverse health effects, poorer neurobehavioral development, reproductive disorders, congenital malformations and genotoxicity have been reported for residents of flower production areas and workers throughout the flower production cycle. Studies including water samples show overuse of pesticides, while environmental impacts are related to water and air contamination, soil degradation and adverse effects on the reproduction and development of non-target organisms. This review points out that the absence of MRL for non-edible flowers can be crucial for the trade of contaminated products across borders, including pesticides banned in importing countries. Furthermore, setting limits on flowers could reduce the use of pesticides in producing countries.
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•Latin America has a high scientific production on pesticides in flower production.•Two hundred pesticides were identified by interviews and analytical measurements.•Importing countries do not set limits on pesticides in ornamental flowers.•Pesticide limits in flowers should reduce human exposure in exporting countries.•Cross-border trade of contaminated flower products deserves special attention.
Setting pesticide limits for ornamental flowers can reduce human exposure and environmental contamination in producing countries and restrict cross-border trade in contaminated products.
Until the 1990s the 1,1,1-trichloro-bis-2,2′-(4chlorophenyl) ethane (DDT) was sprayed in the walls of the house along the Madeira River basin, Brazilian Amazon, a region well known for its large ...number of malaria cases. In 1910, Oswaldo Cruz described the presence of malaria in 100% of the population living in some localities from the Madeira River basin. Data available in the literature point to the DDT contamination in fishes captured in Madeira River region. Fish is the major source of dietary protein to these people. DDT tends to accumulate in lipid rich tissues and is being eliminated by different events, including lactation. Considering the importance of feeding breast milk to the children, the associated risks of DDT exposure via breast milk intake to children must be assessed. This is the main objective of this work: to analyse the presence of the
p,
p′-DDT and its metabolites
p,
p′-DDE and
p,
p′-DDD in 69 human milk samples and to estimate the intake of DDT and its metabolite in terms of total DDT (total DDT
=
p,
p′-DDE
+
p,
p′-DDD
+
p,
p′-DDT). All the samples showed contamination with DDT and its metabolites ranging from 25.4 to 9361.9
ng of total DDT/g of lipid (median
=
369.6
ng of total DDT/g of lipid) and 8.7% of the estimated daily intake (EDI), in terms of total DDT, which was higher than the acceptable daily intake proposed by the WHO.
The scope of this work was to evaluate the levels of polycyclic aromatic hydrocarbons (PAHs) and their possible sources in two shallow sediment cores from an estuarine area located in the south ...region of Brazil, the Guaratuba Bay. The estuary is encompassed by an Environmental Protection Area (EPA) of 1306
km
2, which is still considered to be pristine, despite recent urban growth. To assess levels of 14 selected PAHs in the sediments, among those listed as “priority pollutants” by the US Environmental Protection Agency, the cores were divided in several sections, followed by extraction, clean-up, fractionation and subsequent analysis using HPLC coupled to a fluorescence detector. Among the PAHs detected, phenanthrene and fluoranthene showed the highest concentrations. PAHs with more than four rings were usually present in low concentrations or were undetectable. To assist in the identification of possible sources, the ratios An/(An
+
Phe) and Flt/(Flt
+
Py) (anthracene to anthracene plus phenanthrene and fluoranthene to fluoranthene plus pyrene) and a PCA model were also used. Total concentrations of PAHs ranged between 1.5 and 3130
ng/g (mean 495) dry weight for the core collected in the inner part of the estuary, and between 78.5 and 3270
ng/g (mean 899) dry weight for the other core, collected in the outer part. Compared to values found in other studies in coastal zones along South American eastern margin, this area can be considered to range from low polluted to moderately polluted. From the data, it was also possible to conclude that there is predominance of petroleum sources, and essentially close to the more urbanised areas. Combustion sources have only minor contribution and are episodic, when compared to the latter.
Especially added on many industrial and domestic products as flame retardants (FRs), polybrominated diphenyl ethers (PBDEs) are among the chemicals of high environmental concern because of their ...potential harmfulness for environmental and human health. Seafood consumption is considered the main source of PBDEs and their methoxylated congeners (MeO-BDEs) for humans. The present study aims to investigate the seasonal occurrence of six PBDEs and eight MeO-BDEs congeners using Douro river biota (different trophic levels) as sentinels, as well as to evaluate the human exposure risk to PBDEs through seafood consumption. Biota samples (n = 273) were collected from one of the most important Portuguese estuaries in the north-western coast of Portugal at four different seasons (2019–2020). The analyses were performed by an environmental-friendly extraction procedure followed by Gas Chromatography coupled to a triple quadrupole detector (GC–MS/MS). PBDEs were detected in all seafood samples analysed, with means ranging from 0.02 ng g−1 ww (flounder in autumn) to 3.75 ng g−1 ww (mussel in winter). Levels of lower-brominated PBDE congeners were significantly higher than higher-brominated ones in all seasons (p < 0.01). MeO-BDEs ranged from 0.001 ng g−1 ww (grey mullet in summer) to 5.66 ng g−1 ww (green crab in spring). Crabs and mussels presented the highest means of PBDEs and MeO-BDEs. Regarding the health risk assessment of the studied PBDE congeners (47, 99, and 153), consumption of Douro river fish is not a case of concern for consumers.
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•PBDEs and their metabolites were found in Douro river biota.•Higher levels of MeO-BDEs were found in both invertebrate and macroalgae species.•PBDEs and MeO-BDEs levels varied among seasons.•Low risk through fish consumption according to the MOE threshold for PBDEs.
Thermostability is an important and desired feature of therapeutic proteins and is critical for the success or failure of protein drugs development. It can be increased by PEGylation-binding of ...poly(ethylene glycol) moieties-or glycosylation-post-translational modification to add glycans. Here, the thermostability and thermodynamic parameters of native, PEGylated, and glycosylated versions of the antileukemic enzyme crisantaspase were investigated. First-order kinetics was found to describe the irreversible deactivation process. Activation energy of the enzyme-catalyzed reaction (E*) was estimated for native, PEGylated, and glycosylated enzyme (10.2, 14.8, and 18.8 kJ mol
−1
respectively). Half-life decreased progressively with increasing temperature, and longer half-life was observed for PEG-crisantaspase (87.74 min) at 50 °C compared to the native form (9.79 min). The activation energy of denaturation of PEG-crisantaspase (307.1 kJ mol
−1
) was higher than for crisantaspase (218.1 kJ mol
−1
) and Glyco-crisantaspase (120.0 kJ mol
−1
), which means that more energy is required to overcome the energy barrier of the unfolding process. According to our results, PEG-crisantaspase is more thermostable than its native form, while Glyco-crisantaspase is more thermosensitive.
The determination of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in raw cow milks have never been reported in Brazil. Since the consumption of food of animal ...origin, including milk and dairy products, is the major source of human exposure to these compounds, this study aimed to establish the levels and profile of seven PCDDs and ten PCDFs in raw cow milk samples collected in eight Brazilian states which among the major milk producer states. Raw milk samples were collected in 34 different dairy cattle farms during the summer of 2013. All PCDD/Fs congeners were found at least in some of the 34 samples studied. The octa-chlorinated congeners (OCDD and OCDF) were ubiquitous and also present in high concentrations. The mean values of WHO-TEQ1998;2005 were respectively 1.66 and 1.36pgTEQg−1 fat and samples taken in São Paulo showed the highest WHO-TEQ values (2.46 TEQ1998g−1 fat and 2.10pgTEQ2005g−1 fat). Although all samples showed some contamination level, all values were below the limit established by European Union for total PCDD/Fs in cow milk (3pgWHO-TEQ1998g−1 fat). Principal Component Analysis (PCA) showed that OCDD and OCDF were responsible for 73% and 20% of the total data variance, respectively and they presented an independent behavior, probably as a result of distinct origins. The use of TEQ as weights in the PCA, revealed the importance of the penta-chloro congeners and it was possible to identify sample distribution patterns probably associated with the main PeCDD and PeCDF. The importance of local sources to PCDD/Fs concentrations is still to be evaluated and determined.
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•Selected (2,3,7,8-substituted) PCDD/Fs were determined in Brazilian raw cow milks.•All samples of Brazilian cow milk contained some or all 2,3,7,8-substituted PCDD/Fs at some level.•PCDD/Fs concentrations in Brazilian cow milk were below the limit established by EU.
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