Endocrine disrupting chemicals removal in an aerobic granular sludge reactor treating simulated saline wastewater

The occurrence of Endocrine disrupting chemicals (EDCs) in the environment is a topic of concern. It is commonly accepted that the major source of EDCs to the environment is wastewater treatment plants effluents. Salinity is an additional common stress factor in wastewater treatment. Aerobic granular sludge (AGS) has a number of properties that make it more attractive than conventional biological systems for treatment of wastewater containing EDCs. In the present study, an AGS sequencing batch reactor adapted to salinity was operated for 140 days for treating synthetic saline wastewater containing 17β–estradiol (E2), 17α–ethinylestradiol (EE2) and bisphenol-A (BPA). E2 was removed by biodegradation. EE2 adsorption/desorption to the aerobic granules was observed. The increasing of BPA removal efficiency after bioaugmentation with a degrading bacterial strain shows that biodegradation was the removal mechanism. COD removal was not significantly affected by EDCs shock loads. Activity of ammonia oxidizing bacteria and nitrite oxidizing bacteria did not seem to be inhibited by the presence of EDCs. The activity of phosphate accumulating organisms was affected.info:eu-repo/semantics/publishedVersio

Improving the downstream processing of interferon alfa-2b using alternative purification platforms based on ionic liquids

Improvements on human life expectancy and the lack of effective therapies has led to an increment of chronic diseases, being the application of biopharmaceuticals an efficient strategy to mitigate this scenario. Among the current available biopharmaceuticals, the role of interferon α-2b (IFNα-2b) should be highlighted, as it has been marketed over 30 years with a considerable impact on the global therapeutic proteins market (Castro et al, Vaccines, 2021). IFN manufacturing requires the use of the recombinant DNA technology, involving two main stages, the upstream and downstream stages. The first includes recombinant protein production in a suitable host microorganism, such as Escherichia coli (Castro et al, Sep. Purif. Technol., 2020), while the second comprises protein recovery, isolation, purification and polishing. Due to the high demands of the pharmaceutical industry for products with high purity and biological activity, the downstream stage is responsible for the majority of the production costs of biopharmaceuticals (50–90%), often including time-consuming and multi-step processes. Therefore, there is an immediate need to develop more efficient, cost-effective, and sustainable protein purification methodologies. In this work, two ionic-liquid-(IL)-based strategies were investigated for the purification of IFNα-2b recombinantly produced from E. coli fermentation broth, namely as adjuvants in aqueous biphasic systems or as chromatographic ligands immobilized in solid materials. Overall, the obtained results demonstrate that by tailoring IL’s chemical structures, improved protein purification processes are obtained and that the secondary structure of proteins is preserved.publishe

Sustainable ionic-liquid-based strategies for the downstream processing of interferon α-2b from Echerichia coli

Over the last decades, society has been facing an increment of chronic diseases due to the higher human life expectancy and the lack of efficient treatments for several pathologies. In this regard, biopharmaceuticals have become one of the most effective clinical treatments for a broad range of diseases, including cancer, metabolic and neurodegenerative disorders [1]. Among biopharmaceuticals, the role of interferons, particularly interferon α-2b (IFNα-2b), should be underlined, as they have been marketed for over 30 years with a considerable impact on the global therapeutic proteins market [2]. Usually based on the recombinant DNA technology, the manufacturing process of biopharmaceuticals encompasses two main stages: the upstream and downstream stages. Typically, the upstream phase includes recombinant protein production processes in a suitable host microorganism, such as Escherichia coli [3], while the general downstream processing of biopharmaceuticals comprises four stages - recovery, isolation, purification and polishing -, which are responsible for the majority of the production costs of biopharmaceuticals (50–90%) [3]. The downstream processing is a time-consuming and multi-step process, for which the development of cost-effective purification processes is mandatory to decrease their costs and environmental impact. In this context, two ionic-liquid-(IL)-based strategies were investigated in this work for the purification of IFNα-2b recombinantly produced from E. coli fermentation broth. ILs have been used as adjuvants in aqueous two-phase systems (ATPS) and applied in supported materials as alternative ligands. The obtained results demonstrate that ILs have a tailoring ability and contribute to the development of more effective and sustainable downstream processes of biopharmaceuticals.publishe

Purification of interferon alpha 2b-based biopharmaceuticals using ionic liquid-based technologies

Protein biopharmaceuticals, among which interferon alpha-2b (IFNα-2b) that can be used in the treatment of chronic hepatitis C, have become an indispensable product of current medicine. Aiming at finding new cost-effective, efficient and sustainable technologies for recombinant IFNα-2b purification, ionic liquids were investigated as adjuvants in polymer-polymer aqueous two-phase systems (ATPS) or as chromatographic ligands covalently attached in silica (Supported ionic liquids, SILs). The application of ionic liquids as adjuvants in ATPS composed of polyethylene glycol (PEG 600 g/mol) and polypropylene glycol (PPG 400 g/mol) enhanced the purity of IFNα-2b recovered in the PEG-rich phase. On the other hand, SILs exhibited promising results toward IFNα-2b purification both in conditions favouring ionic or hydrophobic interactions, reinforcing the multimodal character of these novel stationary phases. Also, the secondary structure of IFNα-2b is preserved with both purification processes, as appraised by circular dichroism and western-blot studies. Overall, our results demonstrate the high potential exhibited by ionic liquids toward the preparative purification of the recombinant IFNα-2b biopharmaceuticals.publishe

Bacterial strain rhodococcus sp. ED55 degrades endocrine disrupring chemicals in wastewater

info:eu-repo/semantics/publishedVersio

Rhodococcus sp. ED55: a bacterial strain with ability to degrade endocrine disrupting chemicals and potential for bioaugmentation

The occurrence of Endocrine disrupting chemicals (EDCs) in the environment is a topic of concern. It is commonly accepted that the major source of EDCs to the environment is wastewater treatment plants (WWTPs’) effluents, due to the inefficiency of WWTPs to remove this kind of pollutants. A bacterial strain – Rhodococcus sp. ED55 was isolated from the sediments of a discharge point of a WWTP in Coloane, Macau, for its ability to degrade EDCs. The bacterium was able to biodegrade 17β–estradiol (E2), 17α–ethinylestradiol (EE2), bisphenol-A (BPA) and bisphenol-S (BPS) at different extents. Strain ED55 was able to completely degrade the supplied amount of E2 in few hours, both in synthetic medium and in real wastewater from a municipal WWTP (Parada, Maia – Portugal). Estrone (E1), 4OH-E1 and 4OH-E2 were identified as intermediate degradation metabolites and the metabolic pathway is under elucidation. Bioaugmentation with Rhodococcus sp. ED 55 significantly improved the natural attenuation of the compound in municipal wastewater in batch assays. The acute test with luminescent marine bacterium Vibrio fischeri revealed elimination of the toxicity of the treated effluent and the standardized yeast estrogenic (S-YES) assay with the recombinant strain of Saccharomyces cerevisiae revealed decrease of estrogenic activity of samples. Rhodococcus sp. ED55 was applied in a strategy of an AGS sequencing batch reactor adapted to salinity, which was operated for treating a synthetic saline wastewater containing E2, EE2 and BPA. E2 was no longer detected in the bulk liquid after 10 min of aerobic reaction throughout reactor operation, suggesting that this compound was quickly removed by biodegradation. EE2 adsorption/desorption to the aerobic granules was observed. Removal of BPA significantly increased after bioaugmentation with Rhodococcus sp. ED55, showing that biodegradation was the governing removal mechanism. COD removal was not significantly affected by EDCs shock loads. Rhodococcus sp. ED55 can potentially be applied in bioaugmentation strategies for ameliorating treatment of wastewater contaminated with EDCs.info:eu-repo/semantics/publishedVersio

Transtorno mental comum na gravidez e sintomas depressivos pós-natal no estudo MINA-Brasil: ocorrência e fatores associados

OBJECTIVE To investigate the occurrence and factors associated with common mental disorders in pregnancy and depressive symptoms in postpartum, as well as the association between both in the Brazilian Western Amazon. METHODS This is a prospective cohort in the MINA-Brazil study with women who received primary health care in the town of Cruzeiro do Sul, Acre State. We performed two clinical evaluations during pregnancy (the first: 16–20 weeks; the second: 28 gestational weeks) and three postpartum evaluations (at 3, 6 and 12 months), in which demographic and socioeconomic, gestational, lifestyle and clinical data were collected. We used the Self-Reported Questionnaire (score ≥ 8) to screen the gestational common mental disorder and the Edinburgh Postnatal Depression Scale (score ≥ 10) to identify postpartum depressive symptoms. We used adjusted ordinal logistic regression to investigate the relationship between the covariates and the occurrence of common mental disorders in pregnancy and postpartum depressive symptomatology. RESULTS A total of 461 women completed the two clinical evaluations in pregnancy; of these, 247 completed the three postpartum evaluations. The occurrence of common mental disorder during pregnancy was 36.2% and 24.5% in the first and second evaluations, respectively, and the cumulative incidence was 9.2%. In addition, 50.3% maintained the disorder between evaluations. During postpartum, approximately 20% of the mothers presented depressive symptoms during the first year of their children’s lives. Parity (≥ 2) was associated with common mental disorders, while low maternal education was associated with postpartum depressive symptoms. Women with a common mental disorder in both evaluations during pregnancy were 5.6 times more likely (95%CI: 2.50–12.60) to develop postpartum depressive symptoms. CONCLUSION The occurrence of common mental disorder at any time assessed during pregnancy, but especially its persistence from the second trimester, was strongly associated with depressive symptoms after childbirth. These findings highlight the need for early screening and monitoring of the mental health of pregnant women at the start of prenatal care in order to reduce possible negative impacts on the health of the mother-child binomial caused by such events.OBJETIVO Investigar a ocorrência e os fatores associados com os transtornos mentais comuns na gestação e sintomas depressivos no pós-parto, bem como a associação entre ambos na Amazônia Ocidental Brasileira. MÉTODOS Coorte prospectiva no estudo MINA-Brasil com mulheres atendidas na atenção primária à saúde de Cruzeiro do Sul, Acre. Foram realizadas duas avaliações clínicas na gestação (primeira: 16–20 semanas; segunda: 28 semanas gestacionais) e três avaliações no pós-parto (aos 3, 6 e 12 meses), nas quais foram coletados dados demográficos e socioeconômicos, gestacionais, de estilo de vida e clínicos. Utilizou-se o Self-Reported Questionnaire (escore ≥ 8) para rastreamento do transtorno mental comum gestacional e a escala de depressão pós-natal de Edimburgo (escore ≥ 10) para identificação de sintomas depressivos pós-parto. Foi utilizada regressão logística ordinal ajustada para investigar a relação entre as covariáveis e a ocorrência de transtornos mentais comuns na gravidez e a sintomatologia depressiva no pós-parto. RESULTADOS Um total de 461 mulheres completaram as duas avaliações clínicas na gestação; dessas, 247 completaram as três avaliações pós-parto. A ocorrência de transtorno mental comum durante a gestação foi de 36,2% e 24,5% na primeira e segunda avaliações, respectivamente, e a incidência cumulativa foi de 9,2%. Ademais, 50,3% mantiveram o transtorno entre as avaliações. Durante o pós-parto, aproximadamente 20% das mães apresentaram sintomatologia depressiva ao longo do primeiro ano de vida de seus filhos. A paridade (≥ 2) foi associada ao transtorno mental comum, enquanto a baixa escolaridade materna associou-se com sintoma depressivo pós-parto. Mulheres com transtorno mental comum nas duas avaliações na gravidez apresentaram 5,6 vezes mais chance (IC95% 2,50–12,60) de desenvolverem sintoma depressivo pós-parto. CONCLUSÃO A ocorrência de transtorno mental comum em qualquer momento avaliado durante a gravidez, mas principalmente sua persistência a partir do segundo trimestre, foi fortemente associado ao sintoma depressivo posterior ao parto. Tais achados evidenciam a necessidade de rastreamento precoce e monitoramento da saúde mental de gestantes no início do pré-natal, a fim de reduzir possíveis impactos negativos para a saúde do binômio mãe-filho causados por tais eventos

Functional hybrid nanoemulsions for sumatriptan intranasal delivery

In recent years, advanced nanohybrid materials processed as pharmaceuticals have proved to be very advantageous. Triptans, such as the commercially available intranasal sumatriptan (SMT), are drugs employed in the treatment of painful migraine symptoms. However, SMT effectiveness by the intranasal route is limited by its high hydrophilicity and poor mucoadhesion. Therefore, we designed hybrid nanoemulsions (NE) composed of copaiba oil as the organic component plus biopolymers (xanthan, pectin, alginate) solubilized in the continuous aqueous phase, aiming at the intranasal release of SMT (2% w/v). Firstly, drug-biopolymer complexes were optimized in order to decrease the hydrophilicity of SMT. The resultant complexes were further encapsulated in copaiba oil-based nanoparticles, forming NE formulations. Characterization by FTIR-ATR, DSC, and TEM techniques exposed details of the molecular arrangement of the hybrid systems. Long-term stability of the hybrid NE at 25°C was confirmed over a year, regarding size (~ 120 nm), polydispersity (~ 0.2), zeta potential (~ −25 mV), and nanoparticle concentration (~ 2.1014 particles/mL). SMT encapsulation efficiency in the formulations ranged between 41–69%, extending the in vitro release time of SMT from 5 h (free drug) to more than 24 h. The alginate-based NE was selected as the most desirable system and its in vivo nanotoxicity was evaluated in a zebrafish model. Hybrid NE treatment did not affect spontaneous movement or induce morphological changes in zebrafish larvae, and there was no evidence of mortality or cardiotoxicity after 48 h of treatment. With these results, we propose alginate-based nanoemulsions as a potential treatment for migraine pain.Fil: Ribeiro, Lígia N. M.. Universidade Estadual de Campinas; BrasilFil: Rodrigues da Silva, Gustavo H.. Universidade Estadual de Campinas; BrasilFil: Couto, Verônica M.. Universidade Estadual de Campinas; BrasilFil: Castro, Simone R.. Universidade Estadual de Campinas; BrasilFil: Breitkreitz, Márcia C.. Universidade Estadual de Campinas; BrasilFil: Martinez, Carolina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Igartúa, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Prieto, Maria Jimena. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: de Paula, Eneida. Universidade Estadual de Campinas; Brasi

Epidemiology of Disappearing Plasmodium vivax Malaria: A Case Study in Rural Amazonia

Background: New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings. Methods: Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease. Principal Findings/Conclusions P. vivax prevalence decreased from 23.8% (March–April 2010) to 3.0% (April–May 2013), with no P. falciparum infections diagnosed after March–April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2–3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance