Toward Producing Biopolyethylene/Babassu Fiber Biocomposites with Improved Mechanical and Thermomechanical Properties.

The development of polymeric biocomposites containing natural fibers has grown over the years due to the properties achieved and its eco-friendly nature. Thus, biocomposites involving a polymer from a renewable source (Biopolyethylene (BioPE)) and babassu fibers (BFs), compatibilized with polyethylene grafted with maleic anhydride (MA) and acrylic acid (AA) (PE-g-MA and PE-g-AA, respectively) were obtained using melt mixing and injection molded into tensile, impact, and HDT specimens. Babassu fiber was characterized with Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TGA), and scanning electron microscopy (SEM). The biocomposites were characterized using torque rheometry, TGA, tensile strength, impact strength, thermomechanical properties, Shore D hardness, and SEM. The data indicate that the torque during the processing of compatibilized biocomposites was higher than that of BioPE/BF biocomposites, which was taken as an indication of a possible reaction between the functional groups. Compatibilization led to a substantial improvement in the elastic modulus, tensile strength, HDT, and VST and a decrease in Shore D hardness. These results were justified with SEM micrographs, which showed babassu fibers better adhered to the surface of the biopolyethylene matrix, as well as an encapsulation of these fibers. The system investigated is environmentally sustainable, and the results are promising for the technology of polymeric composites.

Health professionals' recommendations on the use of fluoride varnish for caries prevention in preschool children.

BACKGROUND: Fluoride varnish (FV) is widely recommended for caries prevention in preschool children, despite its anticaries benefits being uncertain and modest. Dentists often report using clinical practice guidelines (CPGs) as a source of scientific information. AIM: To identify and analyze recommendations for clinical practice on the use of FV for caries prevention in preschool children and to assess the methodological quality of the CPG on this topic. DESIGN: Two researchers independently used 12 search strategies and searched the first five pages of Google Search™ and three guideline databases for recommendations freely available to health professionals on the use of FV for caries prevention in preschoolers. Then, they retrieved and recorded recommendations that met the eligibility criteria and extracted the data. A third researcher resolved disagreements. Each included CPG was appraised using the AGREE II instrument. RESULTS: Twenty-nine documents were included. Recommendations varied according to age, patients' caries risk, and application frequency. Of the six CPGs, only one scored above 70% in the AGREE II overall assessment. CONCLUSION: Recommendations on the use of FV lacked scientific evidence, and CPGs were of poor quality. Application of FV is widely recommended despite recent evidence showing an uncertain, modest, and possibly not clinically relevant anticaries benefit. Dentists should be aware that it is necessary to critically appraise CPGs since they may be of poor quality.

Causal validation of the risk for corneal injury in critically ill adults.

BACKGROUND: The validity of a nursing diagnosis depends on a continuous investigation process in different populations to provide clinical evidence. The risk for corneal injury nursing diagnosis was approved in 2013 and only reviewed in 2017, demonstrating the need to perform a clinical validation to improve it. AIM: To perform a causal validation of the risk for corneal injury nursing diagnosis in critically ill adults. STUDY DESIGN: A prospective cohort study was performed in two intensive critical care units in Northern Brazil with adults aged over 18 years without corneal injury at admission. The patients were evaluated for 10 days, using a data collection tool composed of risk factors for the risk for corneal injury nursing diagnosis. The independent variables were described through absolute and relative frequency. The accuracy measures and risk factors were identified through Cox regression, considering a 95% confidence interval. RESULTS: The nurses assessed 209 critically ill adults and identified that 76.0% of them presented the risk for corneal injury nursing diagnosis, with 16.3% developing a corneal injury, all having previously presented the risk for corneal injury nursing diagnosis. The risk factors identified were eyeball exposure (hazard ratio: 1.78; 95% CI: 1.27-2.51), Glasgow score < 6 (hazard ratio: 1.73; 95% CI: 1.15-2.60) and periorbital oedema (hazard ratio: 1.43; 95% CI: 1.03-1.99), with these factors showing high specificity, and the mechanical ventilation variable, showing high sensitivity, with ROC curve of .86. CONCLUSION: Eyeball exposure, Glasgow score < 6 and periorbital oedema are the risk factors of the risk for corneal injury nursing diagnosis, in critically ill adults. These risk factors guide nursing interventions. This causal validation can improve the risk for corneal injury nursing diagnosis levels of evidence in the NANDA International Taxonomy. RELEVANCE TO CLINICAL PRACTICE: It is necessary to guide nursing interventions for critically ill adults with lowered level of consciousness and corneal exposure for the prevention of corneal injury.

Acute and sub-acute toxicity study of ethanol extract from Nectandra leucantha Nees & Mart. (Lauraceae) barks.

Nectandra leucantha has been used in traditional medicine. Several metabolites isolated from N. leucantha extracts displayed immunomodulatory, antileishmanial properties, but the determination of the toxicological profile in mammals has not previously been performed. In this study, the ethanol extract from N. leucantha barks (EENl) was characterized by HPLC/HRESIMS. To study acute toxicity, female mice received EENl in a single dose of 100, 300, 1000, or 2000 mg/kg bw. Later, sub-acute toxicity was introduced in female and male mice by oral gavage at 100, 500 or 1000 mg/kg bw for 28 consecutive days. Hematological and biochemical profiles from the blood as well as histological analysis from the liver and kidney were performed. The HPLC/HRESIMS analysis of the EENl revealed the presence of six neolignans chemically related to dehydrodieugenol B. In the oral acute and sub-chronic studies, EENl did not produce in all doses evaluated any alteration in behavior, biochemical, hematological, body weight gain and food intake or sudden death in Swiss mice. In addition, histopathological data did not reveal any disturbance in liver and kidney morphology after 28 days of EENl treatment. Our results indicate that EENl at dosage levels up to 2000 mg/kg bw is non-toxic and can be considered safe for mammals.

Integrating real-world data from Brazil and Pakistan into the OMOP common data model and standardized health analytics framework to characterize COVID-19 in the Global South.

OBJECTIVES: The aim of this work is to demonstrate the use of a standardized health informatics framework to generate reliable and reproducible real-world evidence from Latin America and South Asia towards characterizing coronavirus disease 2019 (COVID-19) in the Global South. MATERIALS AND METHODS: Patient-level COVID-19 records collected in a patient self-reported notification system, hospital in-patient and out-patient records, and community diagnostic labs were harmonized to the Observational Medical Outcomes Partnership common data model and analyzed using a federated network analytics framework. Clinical characteristics of individuals tested for, diagnosed with or tested positive for, hospitalized with, admitted to intensive care unit with, or dying with COVID-19 were estimated. RESULTS: Two COVID-19 databases covering 8.3 million people from Pakistan and 2.6 million people from Bahia, Brazil were analyzed. 109 504 (Pakistan) and 921 (Brazil) medical concepts were harmonized to Observational Medical Outcomes Partnership common data model. In total, 341 505 (4.1%) people in the Pakistan dataset and 1 312 832 (49.2%) people in the Brazilian dataset were tested for COVID-19 between January 1, 2020 and April 20, 2022, with a median [IQR] age of 36 [25, 76] and 38 (27, 50); 40.3% and 56.5% were female in Pakistan and Brazil, respectively. 1.2% percent individuals in the Pakistan dataset had Afghan ethnicity. In Brazil, 52.3% had mixed ethnicity. In agreement with international findings, COVID-19 outcomes were more severe in men, elderly, and those with underlying health conditions. CONCLUSIONS: COVID-19 data from 2 large countries in the Global South were harmonized and analyzed using a standardized health informatics framework developed by an international community of health informaticians. This proof-of-concept study demonstrates a potential open science framework for global knowledge mobilization and clinical translation for timely response to healthcare needs in pandemics and beyond.

An Integrated Cost Model Based on Real Patient Flow: Exploring Surgical Hospitalization.

Considering the gap observed in studies on health costs, this article aims to propose a cost calculation model for surgical hospitalization. A systematic literature review using PRISMA was conducted to map cost drivers adopted in similar studies and provide theoretical background. Based on the review, an integrated model considering real patient flow was developed using CHEERS guidelines. The micro-costing top-down method was adopted to develop the cost model allowing a balance between the accuracy of the information and the feasibility of the cost estimate. The proposed model fills two gaps in the literature: the standardization of a cost model and the ability to assess a vast number of different surgery costs in the same hospital. Flexibility stands out as an important advantage of the proposed model, as its application enables evaluation of elective and urgent surgeries of medium and high complexity performed in public and private hospitals. As a limitation, the hospital should have hospital information and cost systems implemented. The proposed cost model can provide important information that can result in better decision making. This becomes more relevant in public health, especially in low- and middle-income countries, which faces a lack of resources and whose positive effects can improve healthcare.

Hypericin, a medicinal compound from St. John's Wort, inhibits genotoxicity induced by mutagenic agents in V79 cells.

This study evaluated the cytotoxic, genotoxic, and the modulatory effects on DNA damage of hypericin in Chinese hamster lung fibroblasts (V79 cells). The hypericin is a natural polycyclic quinone, mainly extracted from St. John's Wort (Hypericum perforatum L.). Along with hyperforin, the hypericins are responsible for the antidepressant activity of St. John's Wort. Cytotoxicity was assessed by the XTT colorimetric assay and the nuclear division index (NDI). The genotoxic activity was studied by the micronucleus test at concentrations of 30, 60, 120, and 240 µg/mL. Mutagenic agents, methyl methanesulfonate (MMS, 44 µg/mL), doxorubicin (DXR, 0.5 µg/mL), and etoposide (VP16, 1 µg/mL) were used in combination with different concentrations of hypericin in order to evaluate the modulatory effect on DNA damage. Results showed that the hypericin was cytotoxic at concentrations above 156.2 µg/mL and genotoxic above 120 µg/mL. The hypericin significantly reduced DNA damage frequency induced by DXR, at concentrations of 30 and 60 µg/mL, and MMS at a concentration of 30 µg/mL, but was unable to reduce damage when combined with VP-16. These results demonstrate the non-photoactivated hypericin toxicological safety limits, its protective effect on DNA damage and provide a basis for future studies that may characterize better its chemopreventive mechanism.

Watermelon Reduces the Toxicity of Cisplatin Treatment in C57BL/6 Mice with Induced Melanoma.

An alternative to reduce the undesirable effects of antineoplastic agents has been the combination of classical treatments with nutritional strategies aimed at reducing systemic toxicity without decreasing the antitumor activity of already used drugs. Within this context, this study evaluated the possible reduction of toxicity when cisplatin treatment is combined with watermelon pulp juice supplementation in C57BL/6 mice with melanoma. Watermelon is a fruit rich in vitamins, minerals, proteins, lycopene, carotene, and xanthophylls, which has shown effectiveness in the treatment of cardiovascular diseases, weight loss, urinary infections, gout, hypertension, and mutagenicity. The following parameters were analyzed: animal survival, bone marrow genotoxicity, serum creatinine and urea, histopathological features of the tumor tissue, tumor weight and volume, and weight of non-tumor tissues (kidney, liver, spleen, heart, and lung). The results showed that watermelon had no antitumor effect but reduced the toxicity of cisplatin, as demonstrated by an increase in the number of bone marrow cells and a decrease in serum creatinine and urea levels. The data suggest that watermelon pulp juice can be an alternative for reducing the side effects of antineoplastic agents.

Head and Face Injuries in Brazilian Homicide Victims - A Retrospective Study.

INTRODUCTION: Violence is a serious problem in view of its magnitude and impact on the health of the population in several countries. The aim of the study was to evaluate the occurrence of head and face injuries among homicide victims in a municipality in the Northeastern region of Brazil. MATERIALS AND METHODS: A cross-sectional study carried out at the Police Station for Crimes against Persons of the Civil Police, which evaluated 168 police inquiries of homicide victims notified from January 2015 to December 2018. Variables analyzed were related to the Victim's sociodemographic profile, homicide characteristics and body region involved. Descriptive data analysis and Pearson's Chi-square test (P < 0.05) were performed. RESULTS: There was greater involvement of men (92.9%) aged 20-29 years (36.3%), drug users (70.7%) and with a criminal record (65.9%). There was a predominance of simple homicides (92.3%), with greater occurrence on Sundays (16.7%), in the night shift (40.1%), revenge was the main reason for the crime (32%), and firearms as the main means used (89.2%). Regarding the number of body regions affected, victims were more frequently affected in 2 regions (36.5%). Head injuries were identified in 68.3% of victims, while face injuries represented 35.3%. There was an association between the presence of head injuries and number of injuries (P < 0.05). DISCUSSION: The prevalence of head and face injuries resulting from homicide was high and victims are predominantly young men, drug users and those with a criminal record. The association was found between the presence of head injuries and number of injuries.

Photodynamic and Sonodynamic Therapy with Protoporphyrin IX: In Vitro and In Vivo Studies.

Sono-photodynamic therapy is a promising anticancer technique based on the combination of sonodynamic and photodynamic therapy to improve the cancer treatment effectiveness. This study was aimed at analyzing the effects of the sono-photodynamic (SPD) activity on protoporphyrin IX (PpIX) solution and PpIX-loaded rat liver. In vitro, PpIX 5 µM solutions were irradiated with light (635 nm, 30-50 mW/cm2), ultrasound (1 MHz, 1-2 W/cm2) and both. The PpIX absorption spectra recorded over exposure time revealed that the PpIX decay rate induced by SPD activity (combined irradiation) was approximately the sum of those induced by photodynamic and sonodynamic activity. In vivo, rats were intraperitoneally injected with 5-aminolevulinic acid at the dose of 500 mg/kg weight. After 3 h of injection, the PpIX-loaded livers were irradiated with light (635 nm, 180 ± 9 J/cm2), ultrasound (1.0 MHz, 770 ± 40 J/cm2) and both using a single probe capable of illuminating and sonicating the liver simultaneously. After 30 h, the liver damage induced by each protocol was analyzed histologically. It was found that a greater necrosis depth was induced by the SPD activity. These results suggest that the SPD activity could improve the PpIX decay rate and have greater scope than photodynamic or sonodynamic activity. Further studies should be performed to gain a better understanding of this protocol.

Structure-activity relationship study of cytotoxic neolignan derivatives using multivariate analysis and computation-aided drug design.

Dehydrodieugenol B and five related natural neolignans were isolated from the Brazilian plant species Nectandra leucantha. Three of these compounds were shown to be active against murine (B16F10) and human (A2058) melanoma cells but non-toxic to human fibroblasts (T75). These results stimulated the preparation of a series of 23 semi-synthetic derivatives in order to explore structure-activity relationships and study the biological potential of these derivatives against B16F10 and A2058 cell lines. These structurally-related neolignan derivatives were analyzed by multivariate statistics and machine learning, which indicated that the most important characteristics were related to their three-dimensional structure and, mainly, to the substituents on the neolignan skeleton. The results suggested that the presence of hydroxyl or alkoxyl groups at positions 3, 4 and 5 (with appropriate sidechains) promoted an increase in electropological and charge density, which seem to be important for biological activity against murine (B16F10) and human (A2058) melanoma cells.

Lapachol acetylglycosylation enhances its cytotoxic and pro-apoptotic activities in HL60 cells.

Lapachol is a plant-derived naphthoquinone that kills several types of cancer cells. Derivatives of this molecule may therefore prove to be useful chemotherapeutic agents. In this study, we explored whether glycosylation increases the cytotoxic potency of lapachol towards HL-60 human leukemia cells. Two beta-glycosides were synthesized and characterized: LA4A (lapachol-ß-glucoside) and LA4C (lapachol-N-acetylglucosamine-ß-glucoside). The sugar moieties of both novel molecules were per-acetylated to facilitate cellular uptake. The IC50 values (in µM) for LA4A (5.7) and LA4C (5.3) were lower than those for lapachol (25). LA4A and LA4C triggered typical signs of apoptosis, such as the exposure of phosphatidylserine on the outside of cells, chromatin condensation, DNA fragmentation and a decrease of the mitochondrial transmembrane potential (ΔΨm) prior to cell lysis. Moreover, DNA fragmentation triggered by the lapachol-glycosides was reduced by pre-treatment with the caspase inhibitor, z-VAD-fmk. While LA4A and LA4C activated caspases-3, -8 and -9, lapachol failed to activate these apoptotic proteases, even when used at high concentrations. Finally, the toxicity of lapachol and its derivatives was also tested on non-tumor cells. We used human peripheral neurons (PeriTox test) to evaluate the side effect potential of these compounds. LA4C was clearly less toxic than LA4A. We conclude that LA4C had the most favorable profile as drug candidate (high tumor cell toxicity, reduced neurotoxicity). In general, this study shows that the cytotoxicity of lapachol towards HL-60 can be enhanced by glycosylation, and that the therapeutic ratio may be modified by the type of sugar added.

Fluoride Varnish and Dental Caries in Preschoolers: A Systematic Review and Meta-Analysis.

The aim of this study was to assess the effectiveness of fluoride varnish (FV) in reducing dentine caries at the patient, tooth, and surface levels as well as caries-related hospitalizations in preschoolers. We performed a systematic review of clinical trials of FV, alone or associated with an oral health program, compared with placebo, usual care, or no intervention. Bibliographical search included electronic searches of seven databases, registers of ongoing trials, and meeting abstracts, as well as hand searching. We performed random-effects meta-analyses and calculated confidence and prediction intervals. The search yielded 2,441 records; 20 trials were included in the review and 17 in at least one meta-analysis. Only one study had low risk of bias in all domains. We found no study reporting on caries-related hospitalizations. At the individual level, the pooled relative risk was 0.88 (95% confidence interval [CI] 0.81, 0.95); this means that in a population of preschool children with 50% caries incidence, we need to apply fluoride varnish in 17 children to avoid new caries in one child. At the tooth level, the pooled weighted mean difference was -0.30 (95% CI -0.69, 0.09) and at the surface level -0.77 (95% CI -1.23, -0.31). Considering the prediction intervals, none of the pooled estimates were statistically significant. We conclude that FV showed a modest and uncertain anticaries effect in preschoolers. Cost-effectiveness analyses are needed to assess whether FV should be adopted or abandoned by dental services.

A semi-synthetic neolignan derivative from dihydrodieugenol B selectively affects the bioenergetic system of Leishmania infantum and inhibits cell division.

Leishmaniasis is a neglected disease that affects more than 12 million people, with a limited therapy. Plant-derived natural products represent a useful source of anti-protozoan prototypes. In this work, four derivatives were prepared from neolignans isolated from the Brazilian plant Nectandra leucantha, and their effects against intracellular amastigotes of Leishmania (L.) infantum evaluated in vitro. IC50 values between 6 and 35 µM were observed and in silico predictions suggested good oral bioavailability, no PAINS similarities, and ADMET risks typical of lipophilic compounds. The most selective (SI > 32) compound was chosen for lethal action and immunomodulatory studies. This compound caused a transient depolarization of the plasma membrane potential and induced an imbalance of intracellular Ca2+, possibly resulting in a mitochondrial impairment and leading to a strong depolarization of the membrane potential and decrease of ATP levels. The derivative also interfered with the cell cycle of Leishmania, inducing a programmed cell death-like mechanism and affecting DNA replication. Further immunomodulatory studies demonstrated that the compound eliminates amastigotes via an independent activation of the host cell, with decrease levels of IL-10, TNF and MCP-1. Additionally, this derivative caused no hemolytic effects in murine erythrocytes and could be considered promising for future lead studies.

Genotoxic and cytotoxic effects of neolignans isolated from Nectandra leucantha (Lauraceae).

In this work was evaluated the cytotoxic activity of dehydrodieugenol B (1) and methyldehydrodieugenol B (2) isolated from Nectandra leucantha (Lauraceae) through cytokinesis-block micronucleus (CBMN) and Comet assay. Compounds 1 and 2 displayed in vitro toxicity against human melanoma cells (SKMEL-147) with IC50 values of 4.4 and 43.6 µg/mL, respectively. The interaction of these compounds with resistant human melanoma cell line SKMEL-29 was also investigated. Obtained results showed a concentration-response relationship for DNA damage (DI and D%) in SKMEL-29 cells for compounds 1 and 2 causing an increase in DNA damage on their lower concentrations. Concerning the cytokinesis-block micronucleus cytome (CBMNCyt) assay, all treatments demonstrated an increase in cytostatic and cytotoxic indexes. In micronucleus quantification, compound 1 displayed higher index in comparison to control. Regarding necrotic and apoptotic cells, treatments with SKMEL-29 cells demonstrated 100% of cell death induced by compounds 1 and 2 at 25 and 88 µg/mL, respectively. Additionally, it was observed that apoptosis is prevalent in SKMEL-147 cells treated with compound 1, while necrotic cells were observed in SKMEL-29 cells treated with both compounds. In conclusion, compounds 1 and 2 are suggested as promising cytotoxic agents against human melanoma resistant cells, emphasizing the potential use of these neolignans for the treatment of melanoma.

Chemical Structure and Localization of Levan, the Predominant Fructan Type in Underground Systems of Gomphrena marginata (Amaranthaceae).

Gomphrena marginata Seub. (Amaranthaceae) is an endemic species from Brazilian campos rupestres with a fructan accumulating underground reserve system. Analyses of high performance anion exchange chromatography (HPAEC-PAD) revealed the presence of the soluble carbohydrates glucose, fructose, sucrose, 1-kestose, 6-kestose, nystose and fructans with degree of polymerization (DP) up to approximately 40 fructose units. Data of 1H and 13C Nuclear Magnetic Resonance (NMR) spectroscopy, including Heteronuclear Single-Quantum Correlation (HSQC) and Heteronuclear Multiple-Bonds Correlation (HMBC) showed the presence of ß (2,6) linkages, characteristic of the linear molecule of levan-type fructan(2,6). These results confirmed previous studies suggesting that the reserve carbohydrate in the underground system of this species was levan-type fructans, similar to that of G. macrocephala. Structural analyses of the thickened underground system using light microscopy revealed a mixed origin system consisting mainly of a gemmiferous tuberous root with the upper region formed by short branched stems, both presenting vascular cylinders with unusual growth patterns. Fructan spherocrystals were visualized under polarized light and scanning electron microscopy (SEM) mostly in the cortex and vascular cylinder in both thickened stem and root. In addition to data reported in the literature concerning the occurrence of fructans in the Amaranthaceae, the results presented here suggest that fructans are a trait in this family while the levan-type fructan prevail in Gomphrena species.

Cobertura de hidrofibra com carboximetilcelulose (Aquacel Ag®) em pacientes queimados: Um relato de caso / Hydrofiber dressing with carboxymethylcellulose (Aquacel Ag®) in burn patients: A case report / Curativo de hidrofibra con carboximetilcelulosa (Aquacel Ag®) en pacientes quemados: Un relato de caso

Introdução: O tratamento de queimaduras sempre foi um grande desafio devido aos diferentes níveis de gravidade das lesões. Neste contexto, coberturas modernas a base de prata estão sendo cada vez mais utilizadas nesses pacientes. Relato de Caso: Descrever os benefícios do curativo Aquacel Ag® em lesões por queimadura de 2º grau profundo e 3º grau em paciente atendida na Unidade de Tratamento de Queimados em um hospital de referência em queimaduras e trauma. A paciente teve várias perdas de enxertia devido a quadros infecciosos, sendo a infecção uma das principais variáveis que atrasam a enxertia cutânea. Quando foi introduzido o Aquacel Ag® no tratamento, observou-se melhora da área a ser enxertada. O Aquacel Ag® em queimaduras parciais garantiu menor tempo de cicatrização, melhor resposta à dor, custo e efetividade em relação a outras coberturas, tempo de trabalho de enfermagem, maior conforto na hora da troca de curativo. Considerações Finais: O Aquacel Ag® mostrou-se uma boa escolha de cobertura para queimaduras de espessura parcial, um grande aliado para preparo de lesões de 3º grau para enxertia, além de promover outros benefícios ao paciente.

Introduction: The treatment of burns has always been a great challenge due to the different severity levels of the lesions. Taking this into consideration, modern silver-based wound dressings has been increasingly used in these patients. Case Report: To describe the benefits of the Aquacel Ag® dressing in burn lesions of 2nd and 3rd grade in patients treated at the Burn Treatment Unit in a reference hospital in burns and trauma. The patient had several grafting losses due to infectious conditions, with infection being one of the main variables that delay skin grafting. When Aquacel Ag® was introduced in the treatment, improvement of the area to be grafted was observed. The Aquacel Ag® in partial burns, guaranted a shorter healing time, better response to pain, cost and effectiveness in relation to other coverages, nursing work time, and greater comfort at the time of dressing change. Final Considerations: Aquacel Ag® has been shown to be a good choice of coverage for partial thickness burns, a great ally for the preparation of 3rd degree lesions for grafting, in addition to promoting other benefits to the patient.

Introducción: El tratamiento de quemaduras siempre ha sido un gran desafío debido a los diferentes niveles de gravedad de las lesiones. En este contexto, las cubiertas modernas a base de plata se están utilizando cada vez más en estos pacientes. Relato de Caso: Describir los beneficios del curativo Aquacel Ag® en lesiones por quemadura de 2º grado profundo y 3º grado en paciente atendida en la Unidad de Tratamiento de Quemados en un hospital referencia en quemaduras y trauma. La paciente tuvo varias pérdidas de injerto debido a cuadros infecciosos, siendo la infección una de las principales variables que retrasan la injerto cutáneo. Cuando se introdujo el Aquacel Ag® en el tratamiento, se observó una mejora del área a ser injertada. El Aquacel Ag® en quemaduras parciales garantizó un menor tiempo de cicatrización, mejor respuesta al dolor, costo y efectividad en relación a otras coberturas, tiempo de trabajo de enfermería, mayor confort a la hora del cambio de curativo. Consideraciones finales: Aquacel Ag® se mostró una buena elección de cobertura para quemaduras de espesor parcial, un gran aliado para la preparación de lesiones de 3º grado para injerto, además de promover otros beneficios al paciente.

Neolignans from leaves of Nectandra leucantha (Lauraceae) display in vitro antitrypanosomal activity via plasma membrane and mitochondrial damages.

Chagas disease is a neglected tropical disease, caused by the protozoan parasite Trypanosoma cruzi, which affects more than eight million people in Tropical and Subtropical countries especially in Latin America. Current treatment is limited to nifurtimox and benznidazole, both with reduced effectiveness and high toxicity. In this work, the n-hexane extract from leaves of Nectandra leucantha (Lauraceae) displayed in vitro antitrypanosomal activity against T. cruzi. Using several chromatographic steps, four related neolignans were isolated and chemically characterized as dehydrodieugenol B (1), 1-(8-propenyl)-3-[3'-methoxy-1'-(8-propenyl)-phenoxy]-4,5-dimethoxybenzene (2), 1-[(7S)-hydroxy-8-propenyl]-3-[3'-methoxy-1'-(8'-propenyl)-phenoxy]-4-hydroxy-5-methoxybenzene (3), and 1-[(7S)-hydroxy-8-propenyl]-3-[3'-methoxy-1'-(8'-propenyl)-phenoxy]-4,5-dimethoxybenzene (4). These compounds were tested against intracellular amastigotes and extracellular trypomastigotes of T. cruzi and for mammalian cytotoxicity. Neolignan 4 showed the higher selectivity index (SI) against trypomastigotes (>5) and amastigotes (>13) of T. cruzi. The investigation of the mechanism of action demonstrated that neolignan 4 caused substantial alteration of the plasma membrane permeability, together with mitochondrial dysfunctions in trypomastigote forms. In silico studies of pharmacokinetics and toxicity (ADMET) properties predicted that all compounds were non-mutagenic, non-carcinogenic, non-genotoxic, weak hERG blockers, with acceptable volume of distribution (1.66-3.32 L/kg), and low rodent oral toxicity (LD50 810-2200 mg/kg). Considering some clinical events of cerebral Chagas disease, the compounds also demonstrated favorable properties, such as blood-brain barrier penetration. Unfavorable properties were also predicted as high promiscuity for P450 isoforms, high plasma protein binding affinity (>91%), and moderate-to-low oral bioavailability. Finally, none of the isolated neolignans was predicted as interference compounds (PAINS). Considering the promising chemical and biological properties of the isolated neolignans, these compounds could be used as starting points to develop new lead compounds for Chagas disease.

Neolignans isolated from Nectandra leucantha induce apoptosis in melanoma cells by disturbance in mitochondrial integrity and redox homeostasis.

Six neolignans including three previously undescribed metabolites: 1-[(7R)-hydroxy-8-propenyl]-3-[3'-methoxy-1'-(8'-propenyl)-phenoxy]-4,5-dimethoxybenzene, 4-hydroxy-5-methoxy-3-[3'-methoxy-1'-(8'-propenyl)phenoxy]-1-(7-oxo-8-propenyl)benzene and 4,5-dimethoxy-3-[3'-methoxy-1'-(8'-propenyl)phenoxy]-1-(7-oxo-8-propenyl)benzene were isolated from twigs of Nectandra leucantha Nees & Mart (Lauraceae) using bioactivity-guided fractionation. Cytotoxic activity of isolated compounds was evaluated in vitro against cancer cell lines (SK BR-3, HCT, U87-MG, A2058, and B16F10), being dehydrodieugenol B and 4-hydroxy-5-methoxy-3-[3'-methoxy-1'-(8'-propenyl)phenoxy]-1-(7-oxo-8-propenyl)benzene the most active metabolites. These compounds displayed IC50 values of 78.8 ± 2.8 and 82.2 ± 3.5 µM, respectively, against murine melanoma. Different in vitro mechanism of induced cytotoxicity for this cell line is proposed for both compounds. Obtained results indicated a remarkable effect during the induction of morphological, biochemical and enzymatic features of apoptosis, such as disruption of mitochondrial membrane potential (ΔΨm), exposure of phosphatidylserine in the outer cell membrane, and genomic DNA condensation and fragmentation. Dehydrodieugenol B induced caspase-3 and PARP activation and 4-hydroxy-5-methoxy-3-[3'-methoxy-1'-(8'-propenyl)phenoxy]-1-(7-oxo-8-propenyl)benzene downregulated the levels of Bcl-2 protein. These effects were accompanied by increased levels of reactive oxygen species as a consequence of mitochondrial damage, followed by F-actin aggregation during the cell death process. Dehydrodieugenol B showed oxidative properties and both compounds, especially 4-hydroxy-5-methoxy-3-[3'-methoxy-1'-(8'-propenyl)phenoxy]-1-(7-oxo-8-propenyl)benzene, displayed potential to alkylate nucleophiles, suggesting an accessory mechanism of tumor-induced cytotoxicity by these metabolites.

Antitrypanosomal activity and evaluation of the mechanism of action of dehydrodieugenol isolated from Nectandra leucantha (Lauraceae) and its methylated derivative against Trypanosoma cruzi.

BACKGROUND: From a previous screening of Brazilian biodiversity for antiprotozoal activity, the hexane extract from leaves of Nectandra leucantha (Nees & Mart.) (Lauraceae) demonstrated activity against Trypanosoma cruzi. Chromatographic separation of this extract afforded bioactive dehydrodieugenol (1). Furthermore, methylated derivative 2 (dehydrodieugenol dimethyl ether) was prepared and also tested against T. cruzi. PURPOSE: To examine the therapeutical potential of compounds 1 and 2 against T. cruzi as well as to elucidate the mechanism of action of bioactive compound 1 against T. cruzi. METHODS/STUDY DESIGN: Crude hexane extract from leaves was subjected to chromatographic steps to afford bioactive compound 1. In order to analyze the effect of additional methyl group in the antiparasitic activity of 1, derivative 2 was prepared (both are no pan-assay interference compounds - PAINS). These compounds were evaluated in vitro against T. cruzi (trypomastigote and amastigote forms) and analyzed for the potential effect in host cells through the production of nitric oxide and reactive oxygen species. Finally, the plasma membrane effect of the most potent compound 1 was investigated in T. cruzi trypomastigotes. RESULTS: Compounds 1 and 2 displayed activity against amastigotes of T. cruzi. Although both compounds promoted activity against intracellular amastigotes, the production of nitric oxide and reactive oxygen species of host cells were unaltered, suggesting an antiparasitic activity other than host cell activation. Considering 1 the most effective compound against T. cruzi, the interference in the plasma membrane of the trypomastigotes was investigated using the fluorescent probe SYTOX® Green. After a short-term incubation, the fluidity and integrity of the plasma membrane was completely altered, suggesting it as a primary target for compound 1 in T. cruzi. CONCLUSION: Compounds 1 and 2 selectively eliminated the intracellular parasites without host cell activation and could be important scaffolds for the search of new hit compounds.