Lichen xanthones as models for new antifungal agents

Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for new antimicrobial compounds plays an important role in current medicinal chemistry research. Inspired by lichen antimicrobial xanthones, a series of novel chlorinated xanthones was prepared using five chlorination methods (Methods A–E) to obtain different patterns of substitution in the xanthone scaffold. All the synthesized compounds were evaluated for their antimicrobial activity. Among them, 3-chloro-4,6-dimethoxy-1-methyl-9H-xanthen-9-one 15 showed promising antibacterial activity against E. faecalis (ATCC 29212 and 29213) and S. aureus ATCC 29213. 2,7-Dichloro-3,4,6-trimethoxy-1-methyl-9H-xanthen-9-one 18 revealed a potent fungistatic and fungicidal activity against dermatophytes clinical strains (T. rubrum, M. canis, and E. floccosum (MIC = 4–8 µg/mL)). Moreover, when evaluated for its synergistic effect for T. rubrum, compound 18 exhibited synergy with fluconazole (ΣFIC = 0.289). These results disclosed new hit xanthones for both antibacterial and antifungal activity.This work was partially supported through national funds provided by FCT/MCTES - Foundation for Science and Technology from the Ministry of Science, Technology, and Higher Education (PIDDAC) and the European Regional Development Fund (ERDF) through the COMPETE - Programa Operacional Factores de Competitividade (POFC) programme, under the Strategic Funding UID/Multi/04423/2013, the projects POCI-01-0145-FEDER-028736 and POCI-01-0145-FEDER-016790 (PTDC/MAR-BIO/4694/2014; 3599-PPCDT) in the framework of the programme PT2020, as well as by the project INNOVMAR - Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, within Research Line NOVELMAR), supported by North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Diana I. S. P. Resende also acknowledge for her grant (NOVELMAR/BPD_2/2016-019) and Patrícia Pereira-Terra for her grant (NOVELMAR/BPD/2017/012)

Halogenated polycyclic aromatic hydrocarbons associated with drinking water disinfection

Introduction: Disinfection by-products (DBPs) have been identified in chlorinated water. This fact justifies the growing concern about the potential health effects of emerging unregulated DBPs, some of which appear to be more genotoxic than the regulated DBPs[1]. Polycyclic aromatic hydrocarbons (PAHs) are among the most persistent contaminants detected in environmental samples such as river sediments and tap water. A few studies have already proven that water disinfection can lead to the formation of halogenated derivatives of PAHs, such as chlorinated and brominated PAHs[2] . The available toxicological studies have shown that these compounds possess, in general, greater mutagenicity than the corresponding parent PAHs. Our research group has also shown that exposure of HepG2 cells to a dose-range of 6-Cl-benzo[a]pyrene (6-ClBaP) and BaP resulted in cytotoxicity above 50 µM and that, at the equimolar doses of 100 and 125 µM, 6-ClBaP was able to induce a significantly higher level of DNA damage than BaP[3] . The present study had two main objectives: 1) identification of the major chlorinated and brominated derivatives of benzo[a]anthracene (BaA) and pyrene (Pyr) formed as disinfection by-products and 2) evaluation of their potential hazard to humans, through the characterization of their potential cytotoxic and genotoxic effects in a human cell line.The authors wish to thank Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa for financial support by the grant BRJ-DSA/2012- Doenças Oncológica

Drinking water contaminants: toxicity of halogenated polycyclic aromatic hydrocarbons

Food may be contaminated with polycyclic aromatic hydrocarbons (PAHs) in the process of smoking or heating. These contaminants or their derivatives can also be present in drinking water when raw water contacts with discharges of untreated industrial/waste water effluents, forest fires or by solubilisation of organic material from contaminated soils. A few studies have shown that water disinfection can lead to halogenated derivatives of PAHs (HPAHs) as chlorinated and brominated derivatives, and there are evidences that these compounds may have greater mutagenicity than the parent PAHs. In this study the cytotoxic and genotoxic effects of chlorinated/brominated derivatives of pyrene (Pyr) and benzo[a]anthracene (BaA), 1-ClPyr, 1-BrPyr and 7-ClBaA, which can be formed as water disinfection by-products, were studied in HepG2 cells to assess their potential hazard to human health. The formation of 1-ClPyr, 1-BrPyr and 7-ClBaA under aqueous disinfection conditions in waters contaminated with Pyr and BaA, was confirmed with an optimized gas chromatography method. Cells exposed (24h) to several concentrations of BaA and 7-ClBaA (1 to 200μM) displayed a dose-related and significant increase of cytotoxicity (neutral red assay) with IC50 values of 3.37 and 12.63µM respectively. For Pyr, 1-ClPyr and 1-BrPyr (10 to 200μM), a lower but significant dose-related cytotoxicity was observed. At non-cytotoxic concentrations (10 and 15µM), 7-ClBaA was able to induce a significantly higher level of oxidative DNA damage in HepG2 cells than its parent compound, as assessed by the FPG-modified comet assay. Under these conditions neither Pyr nor its derivatives were genotoxic. In conclusion, the disinfection process may give rise to genotoxic HPAHs with potential impact on human health and it should be performed in raw waters with minimal content of total organic carbon. In real conditions, humans may be exposed to a mixture of these organic compounds and thus their combined toxic effects should be further evaluated

An Optimal Constitution in a Stochastic Environment

Interest groups ; welfare ; social problems ; economic models

Operational research IO 2021—analytics for a better world. XXI Congress of APDIO, Figueira da Foz, Portugal, November 7–8, 2021

This book provides the current status of research on the application of OR methods to solve emerging and relevant operations management problems. Each chapter is a selected contribution of the IO2021 - XXI Congress of APDIO, the Portuguese Association of Operational Research, held in Figueira da Foz from 7 to 8 November 2021. Under the theme of analytics for a better world, the book presents interesting results and applications of OR cutting-edge methods and techniques to various real-world problems. Of particular importance are works applying nonlinear, multi-objective optimization, hybrid heuristics, multicriteria decision analysis, data envelopment analysis, simulation, clustering techniques and decision support systems, in different areas such as supply chain management, production planning and scheduling, logistics, energy, telecommunications, finance and health. All chapters were carefully reviewed by the members of the scientific program committee.info:eu-repo/semantics/publishedVersio

Avaliação da atividade antioxidante e citotóxico in vitro do óleo essencial de curcuma zedoaria (christm.) Roscoe / Evaluation of in vitro antioxidant and cytotoxic activity of curcuma zedoaria (christm.) Roscoe Essential oil

Curcuma zedoaria (Christm.) Roscoe é uma planta herbácea e rizomatosa da família Zingiberaceae. As folhas e os rizomas do gênero Curcuma são fontes de óleos essenciais utilizados na indústria química, farmacêutica e de alimentos devido a sua ação antioxidante. O óleo essencial de Curcuma zedoaria possui potente atividade citotóxica, antioxidante e inibe a proliferação celular de diversos tipos de cânceres. Apesar da sua importância biológica e econômica verificamos ausência na literatura de ensaios in vitro com método de difusão em culturas de Escherichia coli BW9091 e AB1157 sob a ação de agentes oxidantes (SnCl2 e H2O2) que atacam o DNA cromossômico e nucleotídeos livres e de estudos que descrevam a ação do óleo essencial com o antibiótico amoxicilina. Vale ressaltar que as cepas Escherichia coli AB1157 e BW9091 apresentam, respectivamente, todos os mecanismos de reparos funcionantes para o reparo de DNA e uma deficiência na exonuclease III (xthA-), isto é, deficiência nos sistemas envolvidos na correção de danos oxidativos do DNA por excisão de bases (BER). Já o antibiótico amoxicilina tem mobilizado a atenção e preocupação em serviços hospitalares devido ao aumento de casos de resistência microbiana. Verificou-se, neste estudo que óleo essencial de Curcuma zedoaria inibiu as cepas Escherichia coli BW9091 nas concentrações de 12 e 24 L. Contudo, a diferença na concentração foi, ligeiramente, mais perceptiva em Escherichia coli AB1157 (p<0,001) do que com a Escherichia coli BW9091 (p<0,01). É provável que a presença do gene mutante na cepa Escherichia coli BW9091 tenha promovido um aumento da resistência ao efeito inibitório do óleo essencial. Verificamos que o óleo essencial de Curcuma zedoaria nas concentrações de 24 e 12 µL apresentou potencial inibitório em ambas as cepas de Escherichia coli. Verificou-se, em Escherichia coli AB 1157, que a associação entre o óleo essencial e amoxicilina na concentração de 12 µL apresentou um halo de inibição maior do que quando administrado com o antibiótico isolado. O teste Turkey Kramer demonstrou que houve uma diferença significativa (p<0.001) entre as médias desses halos. A associação de óleo essencial com o cloreto estanoso 12 µL teve seu efeito citotóxico potencializado com ambas as cepas. Entretanto, em Escherichia coli AB 1157 o halo de inibição foi menor, demonstrando que o óleo essencial pode exercer um efeito sinérgico quando associado ao cloreto estanoso. Vale a pena ressaltar que essas diferenças foram significativas (p<0.01) tanto para a Escherichia coli AB1157 e BW9091. Já no controle positivo do peróxido de hidrogênio (H2O2) + 12 µL do óleo essencial observamos aumento na ação oxidativa na cepa AB1157. Portanto, concluímos que o óleo essencial tem potencial farmacológico como princípio ativo natural; exerceu atividades antioxidante e antimicrobiana sobre as cepas de Escherichia coli testadas e potencializou o efeito inibitório quando associado ao antibiótico amoxicilina

Digestible lysine effects on gene expression by Japanese quails in the pre-laying phase

This study aimed to determine the effects of digestible lysine levels in the diets of Japanese quail (Coturnix coturnix japonica) on performance, blood parameters and the expression of insulin-like growth factor I, and growth hormone receptor (GHR), apolipoprotein A-I (APOA-I), acetyl-CoA-carboxylase (ACC), and fatty acid synthase (FAS) genes. A total of 288 seven-day-old female Japanese quails were randomly assigned to one of three diets that contained 0.8%, 1.10%, or 1.40% digestible lysine. The birds were slaughtered at 42 days old, and relative gene expression was evaluated in the liver by qRT-PCR using the 2-ΔCT method. Lysine supplementation had no effect on weight gain and feed conversion. Abdominal fat was lower in birds supplemented with 0.8% digestible lysine than those supplemented with 1.10% and 1.40%. Increased total cholesterol and triglycerides were elevated in quails that received supplementation of 1.10% digestible lysine compared with the other diets. High density lipoproteins were decreased in birds that received 0.8% digestible lysine. Quails fed with 1.40% digestible lysine had greater expression of GHR and APOA-I than quails fed diets with 0.8 and 1.10% (P <0.05). The greatest expressions of ACC and FAS were observed in the liver of quails fed with 0.8% digestible lysine. The current results suggest that lysine supplementation in the pre-laying phase allows birds to deposit muscle mass to reach the optimal conformation and body fatness that provides an energetic reserve for the productive phase by modulating the expression of genes related to growth and lipid metabolism. Keywords: Coturnix coturnix japonica, growth, growth hormone, lipid synthesis, lipid metabolis

Multidisciplinary Experience In The Selection Of Patients For Tubal Sterilization.

Results of the use of a special protocol for evaluation of patients requiring tubal ligation is presented after applied by a multidisciplinary group. The authors conclude that the use of defined parameters of age, parity, marital union duration, number of children alive and the presence of maternal clinical pathology are useful to identify patients with smaller chances of regret after surgery.27% of reproductive-age women in Brazil have chosen surgical sterilization as their contraceptive method. Most of these women who have undergone tubal sterilization opted for cesarean surgery. However, given the young ages of many of these women, many regret having been sterilized. This paper summarizes the experience of a multidisciplinary group in evaluating women who apply for surgical sterilization at the Department of Tocogynecology, Faculdade de Ciencas Medicas, Universidade Estadual de Campinas in Sao Paulo. Detailed descriptions are presented of the medical and social characteristics of cases seen between June 1988 and July 1989. The authors conclude that the use of the defined parameters of age, parity, marital union duration, number of living children, and the presence of maternal clinical pathology are useful in identifying the patients who are least likely to regret undergoing surgical sterilization.113171572