Dibucaine in Ionic-Gradient Liposomes: Biophysical, Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of dibucaine.Fil: Couto, Verônica M.. Universidade Estadual de Campinas; BrasilFil: Prieto, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Igartúa, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Feas, Daniela Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Ribeiro, Lígia N.M.. Universidade Estadual de Campinas; BrasilFil: Silva, Camila M.G.. Universidade Estadual de Campinas; BrasilFil: Castro, Simone R.. Universidade Estadual de Campinas; BrasilFil: Guilherme, Viviane A.. Universidade Estadual de Campinas; BrasilFil: Dantzger, Darlene D.. Universidade Estadual de Campinas; BrasilFil: Machado, Daisy. Universidade Estadual de Campinas; BrasilFil: Alonso, Silvia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: de Paula, Eneida. Universidade Estadual de Campinas; Brasi

Prevalences of hyperhomocysteinemia, unfavorable cholesterol profile and hypertension in European populations

Item does not contain fulltextBACKGROUND: Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular diseases (CVD). HHCY may interact with hypertension (HTEN) and an unfavorable cholesterol profile (UNFAVCHOL) to alter the risk of CVD. OBJECTIVES: To estimate the prevalences of HHCY (1) isolated and (2) in combination with UNFAVCHOL and/or HTEN in different age categories. To provide information that may improve the screening and treatment of subjects at risk of CVD. DESIGN: Cross-sectional data on 12,541 men and 12,948 women aged 20 + y were used from nine European studies. RESULTS: The prevalence of isolated HHCY was 8.5% in subjects aged 20-40 y, 4.7% in subjects aged 40-60 y and 5.9% in subjects aged over 60 y. When combining all age groups, 5.3% had isolated HHCY and an additional 5.6% had HHCY in combination with HTEN and/or UNFAVCHOL. The combinations of risk factors increased with age and, except for HHCY&UNFAVCHOL, were more prevalent than predicted by chance. Of the young subjects (20-40 y), 24% suffered from one or more of the investigated CVD risk factors. This figure was 75.1% in the old subjects (60+ years). CONCLUSIONS: A substantial number of subjects in selected European populations have HHCY (10.9%). In half of these cases, subjects suffer also from other CVD risk factors like UNFAVCHOL and HTEN. Older people in particular tend to have more than one risk factor. Healthcare professionals should be aware of this when screening and treating older people not only for the conventional CVD risk factors like UNFAVCHOL and HTEN but also HHCY, as this can easily be reduced through increased intake of folic acid via supplement or foods fortified with folic acid

Mineralogical and geochemical analysis of Fe-phases in drill-cores from the Triassic Stuttgart Formation at Ketzin CO₂ storage site before CO₂ arrival

Reactive iron (Fe) oxides and sheet silicate-bound Fe in reservoir rocks may affect the subsurface storage of CO2 through several processes by changing the capacity to buffer the acidification by CO2 and the permeability of the reservoir rock: (1) the reduction of three-valent Fe in anoxic environments can lead to an increase in pH, (2) under sulphidic conditions, Fe may drive sulphur cycling and lead to the formation of pyrite, and (3) the leaching of Fe from sheet silicates may affect silicate diagenesis. In order to evaluate the importance of Fe-reduction on the CO2 reservoir, we analysed the Fe geochemistry in drill-cores from the Triassic Stuttgart Formation (Schilfsandstein) recovered from the monitoring well at the CO2 test injection site near Ketzin, Germany. The reservoir rock is a porous, poorly to moderately cohesive fluvial sandstone containing up to 2–4 wt% reactive Fe. Based on a sequential extraction, most Fe falls into the dithionite-extractable Fe-fraction and Fe bound to sheet silicates, whereby some Fe in the dithionite-extractable Fe-fraction may have been leached from illite and smectite. Illite and smectite were detected in core samples by X-ray diffraction and confirmed as the main Fe-containing mineral phases by X-ray absorption spectroscopy. Chlorite is also present, but likely does not contribute much to the high amount of Fe in the silicate-bound fraction. The organic carbon content of the reservoir rock is extremely low (<0.3 wt%), thus likely limiting microbial Fe-reduction or sulphate reduction despite relatively high concentrations of reactive Fe-mineral phases in the reservoir rock and sulphate in the reservoir fluid. Both processes could, however, be fuelled by organic matter that is mobilized by the flow of supercritical CO2 or introduced with the drilling fluid. Over long time periods, a potential way of liberating additional reactive Fe could occur through weathering of silicates due to acidification by CO2

Avaliação genética de populações naturais e de estoques de um programa de repovoamento de pacu (Piaractus mesopotamicus) utilizando marcadores microssatélite

Utilizaram-se marcadores microssatélites para estimar a diversidade genética de grupos de pacu (Piaractus mesopotamicus) coletados nas escadas de transposição das hidroelétricas de Canoas I (CI) e Canoas II (CII), no Rio Paranapanema, e de um estoque e uma progênie utilizados em programas de repovoamento nesse rio. Os loci microssatélites produziram 16 alelos e heterozigosidade observada média similar entre os indivíduos do rio nos dois tempos de coleta (CI14 = 0,7356; CI28 = 0,7361; CII14 = 0,7442; e CII28 = 0,7507), do estoque e da progênie (0,7261 e 0,7287, respectivamente). Foram observados desvios no equilíbrio de Hardy-Weinberg, e valores negativos do índice de fixação com excesso de heterozigotos que indicaram ausência de endogamia. As análises de diversidade genética (distância e identidade genética, índice de Shannon, F ST e AMOVA) foram indicativas de baixa diferenciação genética e conduziram ao agrupamento dos indivíduos do rio, sugerindo que essa espécie está geneticamente estruturada como uma única população. Foram verificados baixa diferenciação genética e altos valores do número de migrantes entre os indivíduos do rio, do estoque e da progênie, o que presume a origem comum derivada dos constantes repovoamentos realizados nesse rio a partir dessas populações estocadas.</jats:p

Tilapicultura semi-intensiva em tanques: Alternativas de fertilização e produção - Revisão

A produção de tilápia tem tido um crescimento acelerado no Brasil e em todo o mundo, principalmente com produções semi-intensivas e intensivas por ser um produto potencialmente disponível para o consumidor, por sua facilidade de cultivo, manejo, alta adaptabilidade, fácil reprodução e alta produtividade. A contínua expansão e melhoramento da efi ciência na tilapicultura requer paralelamente atualização e desenvolvimento de novos conhecimentos e tecnologias que garantem o sustento do produtor aproveitando recursos normalmente perdidos ou inutilizados de uma forma econômica e ecológica, que ofereçam uma alternativa de alimentação e que evitem a contínua contaminação ambiental. O consórcio entre a tilápia, animais domésticos e plantas utilizando resíduos orgânicos como fonte de fertilização e alimentação é uma alternativa viável, ecológica e econômica que fornece ao produtor uma fonte barata de nitrogênio, fósforo e potássio encaminhados à produção primária  o tanque e ao mesmo tempo uma fonte de alimentação de boa qualidade nutritiva que pode substituir a utilização de rações comerciais. Tilapicultura, utilizando água residual e água salgada, são métodos de produção que também tem um grande potencial e que podem ser utilizados pelos produtores no melhoramento e produtividade do cultivo

Genetic Diversity Of Pacu And Piapara Broodstocks In Restocking Programs In The Rivers Paraná And Paranapanema (brazil)

The genetic diversity of Piaractus mesopotamicus (pacu) and Leporinus elongatus (piapara) broodstocks used in restocking programs in the rivers Paraná and Paranapanema is analyzed. One hundred and twenty specimens (two broodstocks of each species) from fish ponds in Palotina PR Brazil and in Salto Grande SP Brazil were assessed. Ten primers produced 96 fragments, comprising 68 (70.83%) and 94 (97.92%) polymorphic fragments for P. mesopotamicus and L. elongatus broodstocks, respectively. Differences (p <0.05) in the frequency of 15 and 27 fragments were detected for each species, without exclusive fragments. Shannon Index (0.347-0.572) and the percentage of polymorphic fragments (57.3%-94.8%) revealed high intra-population genetic variability for all broodstocks. Results of molecular variance analyses (AMOVA) showed that most variations do not lie between the broodstocks but within each broodstock (89%). Genetic (0.088 and 0.142) and identity (0.916 and 0.868) distance rates demonstrated similarity between the broodstocks of each species, corroborated by Fst (0.1023 and 010.27) and Nm (4.18 and 4.33) rates, with a slight genetic difference due to genic flux. High intrapopulation genetic variability and similarity between the broodstocks of each species was also detected, proving a common ancestry.3742365237

Faixa de suficiência para a cultura do algodão no centro-oeste do Brasil: II. micronutrientes

Com o objetivo de estabelecer a faixa de suficiência dos micronutrientes para o algodoeiro, foi utilizado o método da chance matemática para dados de monitoramento nutricional de três localidades produtoras de algodão no cerrado brasileiro, avaliando 152 áreas. O método da chance matemática foi adequado para estabelecer padrões de referência nutricional no algodoeiro, podendo subsidiar parâmetros que a pesquisa convencional não alcançaria em curto espaço de tempo. As faixas encontradas para os micronutrientes com o método da chance matemática tendo como referência a produtividade de 4000kg ha-1 foram, em mg kg-1, de 41-89; 4-14; 90-230; 23-110 e 25-50 para B, Cu, Fe, Mn e Zn, respectivamente, enquanto para a produtividade de 4500kg ha-1 foram, em mg kg-1, de 53-83; 4-12; 110-440; 40-60 e 25-50 para B, Cu, Fe, Mn e Zn, respectivamente. As faixas indicadas, embora semelhantes às recomendações existentes, demonstram aperfeiçoamento para obtenção de altas produtividades. As limitações do método poderão ser atenuadas com a ampliação do sistema de monitoramento nutricional nas lavouras de algodoeiro.For to establish the micronutrients sufficiency range for the cotton, was used the method of mathematical chance for nutritional monitory data of three cotton growth locations in the Midwest of the Brazil, evaluating 152 areas. The method of mathematical chance was adequate for to establish cotton micronutrients references values, can be to help parameters were the conventional research cannot to prove in the short time. The micronutrients sufficiency range for productivity of 4000kg ha-1 were, in the mg kg-1, 41-89; 4-14; 90-230; 23-100; 25-50, and for 4500kg ha-1 was 53-83; 4-12; 110-440; 40-60 e 25-50 for B, Cu, Fe, Mn and Zn, respectively. The sufficiency ranges indicated was similar to the existing official recommendations, however, is indicated the approach for to supply the specifics of the systems. The limitations of the method can be minimized with the expansion of the nutritional monitoring system in the cotton crops

Kaurenoic acid is a potent inhibitor of SARS-CoV-2 RNA synthesis, virion assembly, and release in vitro

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 2019 (COVID-19) pandemic, continues to pose global health challenges despite the availability of approved vaccines and antiviral drugs. The emergence of new variants of SARS-CoV-2 and ongoing post-COVID complications necessitate continuous exploration of effective treatments. Kaurenoic acid (KA) is a tetracyclic diterpenoid isolated from plants of the Copaifera genus and has been previously recognized for its anti-inflammatory, antibacterial, antifungal, and antitumor properties. However, there is a lack of knowledge about the in vitro effects of KA on viruses. Here, we evaluated its effect on SARS-CoV-2 replication for the first time. Methods and Results: KA demonstrated a high selective index of 16.1 against SARS-CoV-2 and robust effectiveness against the B.1.617.2 (Delta) and BA.2 (Omicron) variants. Mechanistically, KA was shown to impair the post-entry steps of viral replication. In a subgenomic replicon system, we observed a decrease in viral RNA synthesis in different cell lines. Using an infectious virus, a larger reduction in the release of SARS-CoV-2 virions was observed. We suggest that KA interacts with SARS-CoV-2 proteases through molecular docking. Conclusion: In conclusion, KA emerges as an inhibitor of SARS-CoV-2 proteases and, consequently, its replication cycle. It could be a good candidate for further investigation in clinical assays against SARS-CoV-2 infection