Diclofenac, ibuprofen, and paracetamol biodegradation: overconsumed non-steroidal anti-inflammatories drugs at COVID-19 pandemic.

The consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have increased significantly in the last years (2020-2022), especially for patients in COVID-19 treatment. NSAIDs such as diclofenac, ibuprofen, and paracetamol are often available without restrictions, being employed without medical supervision for basic symptoms of inflammatory processes. Furthermore, these compounds are increasingly present in nature constituting complex mixtures discarded at domestic and hospital sewage/wastewater. Therefore, this review emphasizes the biodegradation of diclofenac, ibuprofen, and paracetamol by pure cultures or consortia of fungi and bacteria at in vitro, in situ, and ex situ processes. Considering the influence of different factors (inoculum dose, pH, temperature, co-factors, reaction time, and microbial isolation medium) relevant for the identification of highly efficient alternatives for pharmaceuticals decontamination, since biologically active micropollutants became a worldwide issue that should be carefully addressed. In addition, we present a quantitative bibliometric survey, which reinforces that the consumption of these drugs and consequently their impact on the environment goes beyond the epidemiological control of COVID-19.

Anti-Melanogenic Potential of Natural and Synthetic Substances: Application in Zebrafish Model.

Melanogenesis is a biosynthetic pathway for the formation of the pigment melanin in human skin. A key enzyme in the process of pigmentation through melanin is tyrosinase, which catalyzes the first and only limiting step in melanogenesis. Since the discovery of its methanogenic properties, tyrosinase has been the focus of research related to the anti-melanogenesis. In addition to developing more effective and commercially safe inhibitors, more studies are required to better understand the mechanisms involved in the skin depigmentation process. However, in vivo assays are necessary to develop and validate new drugs or molecules for this purpose, and to accomplish this, zebrafish has been identified as a model organism for in vivo application. In addition, such model would allow tracking and studying the depigmenting activity of many bioactive compounds, important to genetics, medicinal chemistry and even the cosmetic industry. Studies have shown the similarity between human and zebrafish genomes, encouraging their use as a model to understand the mechanism of action of a tested compound. Interestingly, zebrafish skin shares many similarities with human skin, suggesting that this model organism is suitable for studying melanogenesis inhibitors. Accordingly, several bioactive compounds reported herein for this model are compared in terms of their molecular structure and possible mode of action in zebrafish embryos. In particular, this article described the main metabolites of Trichoderma fungi, in addition to substances from natural and synthetic sources.

Copaiba essential oil loaded-nanocapsules film as a potential candidate for treating skin disorders: preparation, characterization, and antibacterial properties.

Infections have emerged as a novel target in managing skin and mucosa diseases. Bacterial resistance to antimicrobials and biofilm elimination from surfaces remains a challenge. Because polymeric nanocapsules (NC) can increase antimicrobial activity, this study aimed to produce and characterize NC into chitosan films (CSF). Copaiba essential oil (CO) presents antimicrobial activity and was chosen to load NC. In addition, the antibacterial activity was evaluated to obtain a new biodegradable polymeric platform system with the potential to treat topical diseases associated with bacterial infections. The CO-NC produced by nanoprecipitation presented particle size lower than 250 nm, negative charge, and encapsulation efficiency higher than 70 %. Direct incorporation of CO into CSF (CO-CSF) by casting method worsened the film's characteristics. However, incorporating CO-NC into CSF (CO-NC-CSF) avoided these drawbacks demonstrating improved physical, mechanical, morphological, and topographical properties. FTIR results demonstrated possible intermolecular interactions among the polymers and CO. The CO-NC-CSF and CO-CSF presented antibacterial properties against Staphylococcus aureus, and Pseudomonas aeruginosa, especially the formulation containing 1 % of CO. These results indicated that CO-NC-CSF is a promising candidate for treating skin disorders.

Anti-inflammatory potential of baicalein combined with silk fibroin protein in a zebrafish model (Danio rerio).

Baicalein (BA) is a flavonoid with wide-ranging pharmacological activity. However, its biological evaluation is hampered by its low solubility in aqueous medium, making forms of incorporation that improve its solubility necessary. In the present study, BA was combined with a solution of silk fibroin protein (SF), a biomaterial used too as a drug carrier, to evaluate the anti-inflammatory potential of this combination, in vivo, in an experimental model, zebrafish (Danio rerio). Baicalein-silk fibroin (BASF) improved the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical scavenging rate (95%) in comparison with BA in solution. The acute toxicity study and histopathological analysis in zebrafish showed that BASF has low cytotoxic potential, except for the maxim dose of 2000 mg/kg. The use of BA in combination with SF enhanced the anti-inflammatory effect of flavonoids by inducing inflammatory peritoneal edema through carrageenan and achieved 77.6% inhibition of abdominal edema at a dose of 75 mg/kg. The results showed that the BASF, significantly increases the bioavailability and therapeutic effect of flavonoids and several results observed in this study may help in the development of new drugs.

Euterpe oleracea Mart (Açaizeiro) from the Brazilian Amazon: A Novel Font of Fungi for Lipase Production.

Lipases (EC 3.1.1.3) are hydrolases that catalyze triglycerides hydrolysis in free fatty acids and glycerol. Among the microorganisms that produce lipolytic enzymes, the entophytic fungi stand out. We evaluated 32 fungi of different genera, Pestalotiopsis, Aspergillus, Trichoderma, Penicillium, Fusarium, Colletotrichum, Chaetomium, Mucor, Botryodiplodia, Xylaria, Curvularia, Neocosmospora and Verticillium, isolated from Euterpe oleracea Mart. (Açaizeiro) from the Brazilian Amazon for lipase activity. The presence of lipase was evidenced by the deposition of calcium crystals. The endophytic Pestalotiopsis sp. (31) and Aspergillus sp. (24) with Pz 0.237 (++++) and 0.5 (++++), respectively, were the ones that showed the highest lipolytic activity in a solid medium. Lipase activity was rated in liquid medium, in a different range of temperatures (°C), pH and time (days). The values obtained in the production of lipase by the endophytic fungi were 94% for Pestalotiopsis sp. (31) and 93.87% for Aspergillus sp. (24). Therefore, it is emphasized that the endophytic fungus isolated the E. oleracea palm may be a potential candidate to produce enzymes of global commercial interest.

Mid-term patency of iliac venous stenting for post-thrombotic syndrome.

INTRODUCTION: Post-thrombotic syndrome (PTS) is the most common chronic complication of deep vein thrombosis. Recent studies suggested that iliac stenting in chronic obstructive venous disease is safe and effective. However, systematic reviews focusing on mid-term efficacy of iliac stenting in post-thrombotic syndrome are lacking. This systematic review aimed to analyze mid-term stent patency rates and clinical outcomes of iliac stenting in post-thrombotic syndrome. EVIDENCE ACQUISITION: Two databases were searched: Pubmed/Medline and Scopus. Articles published between January 2000 and July 2020 were selected and titles and abstracts were independently reviewed. Eighteen articles were included for the qualitative analysis. From this initial set of articles, fourteen articles were included for the quantitative analysis. EVIDENCE SYNTHESIS: Overall, 1008 patients were included in this study. The pooled technical success rate was 96%. The pooled primary and secondary patency rates were 98.2% and 100% at 30 days, 78.1% and 94.5% at 12 months and 66.3% and 89.4% at 36 months, respectively. The rates of ulcer healing, pain and edema relief were 78.1%, 53.4% and 48.8%, respectively. The pooled rate of complications including intraoperative venous injury, back pain and stent fracture were 28%, 57.1%, and 5.9%, respectively. CONCLUSIONS: Iliac venous stenting in PTS presents durable mid-term patency rates, as well as significant symptomatic improvement. Therefore, endovascular treatment should be considered in symptomatic patients with PTS.

Development of Quercetin Based Nanodispersions.

Polyphenols are a large group of structurally diverse natural products, including flavonoids. One of the most bioactive compounds of this class is the flavonol quercetin, a recognized antioxidant. Despite several studies were carried out aiming to develop nanoformulations with secondary metabolites, to our knowledge, quercetin was not used as raw material for nanodispersion production without coating polymers. This type of nanosize formulation is often prepared using organic solvents and quercetin nanodispersions were prepared by emulsification evaporation technique, using 1(6).2(2) experimental factorial design, ("surfactant type" evaluated at 6 levels, "surfactant amount" and "stirring speed" evaluated at 2 levels). Variance analysis, after one day of nanodispersions preparation, revealed that only the surfactant type was statistically significant on particle size, while none of factors presented statistically significant effect on polydispersity index. Variance analysis after seven days of nanodispersions preparation revealed that either surfactant type and surfactant amount presented significant effect on particle size, while only surfactant type influenced polydispersity index. Some nanodispersions presented small diameter and narrow size distribution, suggesting potential stability of these systems. Special attention was given to nanodispersion prepared with 3 % (w/w) of polyethylene glycol 400 monooleate (expressed as function of surfactant concentration at aqueous phase). It presented mean droplet size of 129.4 ± 0.5 nm and polydispersity index of 0.173 ± 0.018, after 7 days of preparation. Low polydispersity index indicates a high homogeneity concerning particle size distribution and suggests stability of the system. Moreover, absence of coating polymers and utilization of a low energy method would be an advantage in terms of reducing costs for industrial application, without any nanosize impairment.

Development of a larvicidal nanoemulsion with Copaiba (Copaifera duckei) oleoresin

Copaiba (Copaifera duckei Dwyer, Fabaceae) oleoresin is an important Amazonian raw material. Despite its insecticidal potential, poor water solubility remains a challenge for the development of effective and viable products. Nanotechnology has emerged as a promising area to solve this problem, especially oil-in-water nanoemulsions. On this context, the aim of the present study was to develop oil-in-water nanoemulsions using copaiba oleoresin dispersed through a high internal phase; and evaluate its potential insecticidal action against Aedes aegypti larvae. Overall, 31 formulations were prepared, ranging from 11.5 ± 0.2 to 257.3 ± 4.1 nm after one day of manipulation. Some of them reached small mean droplet sizes (< 200 nm) and allowed achievement of a nanoemulsion region. The formulation consisted of 5% (w/w) of copaiba oil, 5% (w/w) of surfactant and 90% (w/w) of water, which presented mean droplet size of 145.2 ±0.9 nm and polidispersity of 0.378 ± 0.009 after one day of manipulation, and these were evaluated for larvicidal potential. According to mortality level (250 ppm - 93.3 after 48 h), this nanoemulsion was classified as a promising insecticidal agent against Aedes aegypti larvae. The present study allowed the development of low-cost ecofriendly green natural-based nanoformulations with potential larvicidal activity, using a nanobiotechnology approach.

Design of indomethacin-loaded nanoparticles: effect of polymer matrix and surfactant.

Despite recent advances in nonsteroidal anti-inflammatory drug (NSAID) formulations, the design of targeted delivery systems to improve the efficacy and reduce side effects of NSAIDs continues to be a focus of much research. Enteric nanoparticles have been recognized as a potential system to reduce gastrointestinal irritations caused by NSAIDs. The aim of this study was to evaluate the effect of EUDRAGIT® L100, polyethylene glycol, and polysorbate 80 on encapsulation efficiency of indomethacin within enteric nanoparticles. Formulations were developed based on a multilevel factorial design (three factors, two levels). The amount of polyethylene glycol was shown to be the factor that had the greatest influence on the encapsulation efficiency (evaluated response) at 95% confidence level. Some properties of nanoparticles like process yield, drug-polymer interaction, particle morphology, and in vitro dissolution profile, which could affect biological performance, have also been evaluated.

The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst formation is influenced by the lineage of infective Toxoplasma gondii strain.

Toxoplasma gondii strains displaying the Type I/III genotype are associated with acquired ocular toxoplasmosis in humans. Here, we used a mice model to characterize some immunological mechanisms involved in host resistance to infection with such strains. We have chosen the Type I/III strains D8, G2 and P-Br, which cause a chronic infection in mice that resembles human toxoplamosis. Mice deficient of molecules MyD88, IFN-gamma, and IL-12 were susceptible to all three parasite strains. This finding indicates the importance of innate mechanisms in controlling infection. On the other hand, MHC haplotype did not influenced resistance/susceptibility; since mice lineages displaying a same genetic background but different MHC haplotypes (H2b or H2d) developed similar mortality and cyst numbers after infection with those strains. In contrast, the C57BL/6 genetic background, and not MHC haplotype, was critical for development of intestinal inflammation caused by any of the studied strains. Finally, regarding effector mechanisms, we observed that B and CD8+ T lymphocytes controlled survival,whereas the inducible nitric oxide synthase influenced cyst numbers in brains of mice infected with Type I/III strains. These findings are relevant to further understanding of the immunologic mechanisms involved in host protection and pathogenesis during infection with T. gondii.

The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst formation is influenced by the lineage of infective Toxoplasma gondii strain

Toxoplasma gondii strains displaying the Type I/III genotype are associated with acquired ocular toxoplasmosis in humans. Here, we used a mice model to characterize some immunological mechanisms involved in host resistance to infection with such strains. We have chosen the Type I/III strains D8, G2 and P-Br, which cause a chronic infection in mice that resembles human toxoplamosis. Mice deficient of molecules MyD88, IFN-gamma, and IL-12 were susceptible to all three parasite strains. This finding indicates the importance of innate mechanisms in controlling infection. On the other hand, MHC haplotype did not influenced resistance/susceptibility; since mice lineages displaying a same genetic background but different MHC haplotypes (H2b or H2d) developed similar mortality and cyst numbers after infection with those strains. In contrast, the C57BL/6 genetic background, and not MHC haplotype, was critical for development of intestinal inflammation caused by any of the studied strains. Finally, regarding effector mechanisms, weobserved that B and CD8+ T lymphocytes controlled survival,whereas the inducible nitric oxide synthase influenced cyst numbers in brains of mice infected with Type I/III strains. These findings are relevant to further understanding of the immunologic mechanisms involved in host protection and pathogenesis during infection with T. gondii.

Cepas de Toxoplasma gondii que apresentam o genótipo I/III são associadas a toxoplasmose ocular adquirida em humanos. No presente trabalho, nós utilizamos um modelo da doença em camundongos para caracterizar mecanismos imunológicos envolvidos na resistência do hospedeiro à infecção por aquelas cepas. Escolhemos as cepas D8, G2 e P-Br, que causam infecção crônica em camundongos, semelhante à toxoplasmose humana. Camundongos deficientes em MyD88, IFN-G e IL-12 foram susceptíveis a infecções com todas as três linhagens do parasita. Esses dados indicam a importância de mecanismos inatos no controle da infecção. Por outro lado, o haplótipo do MHC não influenciou na resistência/susceptibilidade, na medida em que linhagens de camundongos com um mesmo "background'' genético, mas diferentes haplótipos de MHC (H2b e H2d) apresentam o índice de mortalidade e número de cistos semelhantes após a infecção com aquelas cepas do parasita. Em contraste, o "background'' genético de C57BL/6, mas não o haplótipo de MHC, foi crítico para o desenvolvimento de inflamação intestinal causada pelas cepas estudadas. Finalmente, com relação aos mecanismos efetores, observamos que linfócitos B e T CD8+ controlam a sobrevivência após infecção. Por outro lado, a ativação da enzima óxido nítrico sintase induzida foi um fator importante para controle do número de cistos cerebrais em camundongos infectados com cepas do Tipo I/III. Esses achados são relevantes para o melhor entendimento dos mecanismos imunológicos envolvidos na proteção e patogênese durante infecção com T. gondii.