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Acute gastric variceal bleeding is a life-threatening condition that could be effectively treated with endoscopic cyanoacrylate injection diluted with lipiodol. The mixture acts as a tissue adhesive that polymerizes when in contact with blood in a gastric varix. This work reports a patient that presented to the emergency department with upper gastrointestinal bleeding due to acute variceal bleeding, who developed systemic embolization following cyanoacrylate injection therapy. This complication culminated in cerebral, splenic and renal infarctions with a fatal outcome. Systemic embolization is a very rare, but the most severe complication associated with endoscopic cyanoacrylate injection and should be considered in patients undergoing this treatment.

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ABSTRACT Acute gastric variceal bleeding is a life-threatening condition that could be effectively treated with endoscopic cyanoacrylate injection diluted with lipiodol. The mixture acts as a tissue adhesive that polymerizes when in contact with blood in a gastric varix. This work reports a patient that presented to the emergency department with upper gastrointestinal bleeding due to acute variceal bleeding, who developed systemic embolization following cyanoacrylate injection therapy. This complication culminated in cerebral, splenic and renal infarctions with a fatal outcome. Systemic embolization is a very rare, but the most severe complication associated with endoscopic cyanoacrylate injection and should be considered in patients undergoing this treatment.

RESUMEN La hemorragia digestiva por várices gástricas es una afección potencialmente mortal que puede tratarse eficazmente con la inyección endoscópica de cianoacrilato diluida con lipiodol. La mezcla actúa como un adhesivo tisular que se polimeriza cuando entra en contacto con la sangre de la várice gástrica. Este trabajo nos reporta un paciente que acudió al servicio de urgencias con hemorragia digestiva alta debido a hemorragia aguda por várices, que desarrolló embolización sistémica después de la terapia con inyección de cianoacrilato. Esta complicación culminó en infartos cerebrales, esplénicos y renales con desenlace fatal. La embolización sistémica es una complicación muy rara, pero con alta mortalidad, asociada con la inyección endoscópica de cianoacrilato y debe considerarse en pacientes sometidos a este tratamiento.

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The aim of this work was to evaluate the anti-inflammatory and antioxidant effects of ethyl acetate extract obtained from the leaves of Brazilian peppertree Schinus terebinthifolius Raddi (EAELSt). Total phenols and flavonoids, chemical constituents, in vitro antioxidant activity (DPPH and lipoperoxidation assays), and cytotoxicity in L929 fibroblasts were determined. In vivo anti-inflammatory and antioxidant properties were evaluated using TPA-induced ear inflammation model in mice. Phenol and flavonoid contents were 19.2 ± 0.4 and 93.8 ± 5.2 of gallic acid or quercetin equivalents/g, respectively. LC-MS analysis identified 43 compounds, of which myricetin-O-pentoside and quercetin-O-rhamnoside were major peaks of chromatogram. Incubation with EAELSt decreased the amount of DPPH radical (EC50 of 54.5 ± 2.4 µg/mL) and lipoperoxidation at 200-500 µg/mL. The incubation with EAELSt did not change fibroblast viability up to 100 µg/mL. Topical treatment with EAELSt significantly reduced edema and myeloperoxidase activity at 0.3, 1, and 3 mg/ear when compared to the vehicle-treated group. In addition, EAELSt decreased IL-6 and TNF-α levels and increased IL-10 levels. Besides, it modulated markers of oxidative stress (reduced total hydroperoxides and increased sulfhydryl contents and ferrium reduction potential) and increased the activity of catalase and superoxide dismutase, without altering GPx activity.

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Different degrees in the biological activities of Canavalia rosea had been previously reported . In this study, our group assessed the cardioprotective effects of the ethyl acetate fraction (EAcF) of the Canavalia rosea leaves. Firstly, it was confirmed, by in vitro approach, that the EAcF has high antioxidant properties due to the presence of important secondary metabolites, as flavonoids. In order to explore their potential protector against cardiovascular disorders, hearts were previously perfused with EAcF (300 µg.mL-1) and submitted to the global ischemia followed by reperfusion in Langendorff system. The present findings have demonstrated that EAcF restored the left ventricular developed pressure and decreased the arrhythmias severity index. Furthermore, EAcF significantly increased the glutathiones peroxidase activity with decreased malondialdehyde and creatine kinase levels. EAcF was effective upon neither the superoxide dismutase, glutationes reductase nor the catalase activities. In addition, the Western blot analysis revealed that ischemia-reperfusion injury significantly upregulates caspase 3 protein expression, while EAcF abolishes this effect. These results provide evidence that the EAcF reestablishes the cardiac contractility and prevents arrhythmias; it is suggested that EAcF could be used to reduce injury caused by cardiac reperfusion. However more clinical studies should be performed, before applying it in the clinic.

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Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy.

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The extract obtained from Mikania glomerata leaves rich in ent-kaurenoic acid (ERKA) shows cytotoxic activity in vitro, but its hydrophobic nature and thermosensitivity are issues to be solved prior to in vivo antitumor studies. The purpose of this study was to investigate the antitumor activity of inclusion complexes formed between ERKA and ß-cyclodextrin (ERKA:ß-CD) in rodents. ERKA:ß-CD complexes obtained by malaxation (MX) and co-evaporation (CE) methods were firstly characterized regarding their physical properties, encapsulation efficiency, and cytotoxicity againts L929 cells. The antitumor activity study was then performed in mice with sarcoma 180 treated with saline, 5-fluouracil (5FU) and ERKA:ß-CD at 30, 100 and 300 µg/kg. The weight, volume, percentage of inhibition growth, gross and pathological features and positivity for TUNEL, ki67, NFκB and NRF2 in the tumors were assessed. Serum lactate-dehydrogenase activity (LDH), white blood cells count (WBC) and both gross and pathological features of the liver, kidneys and spleen were also evaluated. The formation of the inclusion complexes was confirmed by thermal analysis and FTIR, and they were non-toxic for L929 cells. The MX provided a better complexation efficiency. ERKA:ß-CD300 promoted significant tumor growth inhibition, and attenuated the tumor mitotic activity and necrosis content, comparable to 5-fluorouracil. ERKA:ß-CD300 also increased TUNEL-detected cell death, reduced Ki67 and NF-kB immunoexpression, and partially inhibited the serum LDH activity. No side effect was observed in ERKA:ß-CD300-treated animals. The ERKA:ß-CD inclusion complexes at 300 µg/kg displays antitumour activity in mice with low systemic toxicity, likely due to inhibition on the NF-kB signaling pathway and LDH activity.

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BACKGROUND: Through new publications on the subject, the main goal of this article is to seek a change in the pattern of alcohol use before and after bariatric surgery. METHODS: We searched the National Library of Medicine, CINAHL, and PsycINFO databases. We included original articles regarding alcohol consumption before and after bariatric surgery to conduct the systematic review. RESULTS: Our systematic review, which included 18 articles, yielded mixed results. Meta-analysis of six articles did not reveal statistically significant differences in alcohol use behaviours before and one year after bariatric surgery. However, throughout the perspective of follow-up after bariatric surgery, nine out of the twelve articles showed improvement in the pattern of alcohol consumption when evaluated up to two years after the end of the surgical period, and four out of the five articles with monitoring beyond two years showed worsening in consumption, compared to pre-surgery alcohol use behaviours. CONCLUSIONS: Conclusions about the relationship between alcohol consumption and bariatric surgery are challenging primarily because of the variety of the methods used and the alcohol consumption measures. Despite that, our research pointed to an increased risk of alcohol use disorders two years after bariatric surgery.

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Alcohol and other drugs treatment includes a wide range of service and personal characteristics, along with expected and unexpected barriers to treatment. To capture the benefits and the gaps of a designed treatment, one needs to consider process-of-care and outcome measurements. Process-of-care measures are mainly developments of the rationale proposed by The Washington Circle and capture all variants in the process-of-care as proportions. Outcome measures are strongly related to different concepts of recovery and described as simple yes/no answers type to wide levels of response, such as in Likert-type scales. According to the studies collected here, more realistic periods of data-collection for process-of-care measures and a more reliable format to capture outcome particularities should be designed.

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Natural polysaccharides are structures composed of highly diversified biological macromolecules whose properties have been exploited by a diversity of industries. Until 2018, the polysaccharides market raised more than US $ 12 billion worldwide, while an annual growth forecast of 4.8% is expected by 2026. The food industry is largely responsible for the consumption of this plant-source material, produced by microbiological fermentation. Among the used polysaccharides, gums are hydrocolloids obtained from a variety of sources and in different forms, being composed of salts of calcium, potassium, magnesium and sugar monomers. Their non-toxicity, hydrophilicity, viscosity, biodegradability, biocompatibility and sustainable production are among their main advantages. Although Brazil is amongst the largest producers of cashew gum, reaching 50 tons per year, the polysaccharide is not being used to its full potential, in particular, with regard to its uses in pharmaceuticals. Cashew gum (CG), obtained from Anacardium occidentale L., caught the attention of the industry only in 1970; in 1990, its production started to grow. Within the Brazilian academy, the groups from the Federal University of Ceará and Piauí are devoting the most efforts to the study of cashew gum, with a total of 31 articles already published. The number of patents in the country for innovations containing cashew tree gum has reached 14, including the technological process for the purification of cashew tree gum, comparison of physical and chemical methods for physicochemical characterizations, and optimum purification methodology. This scenario opens a range of opportunities for the use of cashew gum, mainly in the development of new pharmaceutical products, with a special interest in nanoparticles.

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Background: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.

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BACKGROUND: Solid pseudopapillary neoplasms (SPN) of the pancreas represents approximately 2% of non-endocrine tumors of the pancreas. It is described in the literature as a rare and predominant tumor in young women. AIM: To report a case series with SPN and analyzing clinical, surgical, anatomopathological characteristics, as well as the prognosis and review of literature. METHODS: Retrospective analysis of patients undergoing surgery, with histological diagnosis of SPN between 1998 and 2018, using standardized and prospectively completed forms, performed at the Surgery Service of the Upper Digestive System at Hospital São Rafael/Rede D'Or in Salvador - BA. Review of literature through a database search in MEDLINE/PubMed of retrospective articles. RESULTS: Fourteen female patients with the average age of 31.6 years (range min-max) were selected. Twelve patients (85.7%) were asymptomatic, being an incidental diagnosis or due to screening for other reasons. One patient had abdominal pain due to gastric compression and another patient had jaundice. The 14 patients were staged with computerized tomography or magnetic resonance imaging. None had evidence of metastasis. In 8 patients (57.1%), the tumor was in the tail and body. The average size was 6.7 cm (range min-18). The type of surgery was according to the anatomical location of the tumor. There was no lymph node involvement. In two cases, vascular resection with the use of a prosthesis was required for reconstruction. The surgical margins were free. In all cases, postoperative immunohistochemistry confirmed that it was a solid pseudo-papillary neoplasia of the pancreas. There has been no disease recurrence in any case so far. CONCLUSION: The tumors had a benign, indolent and histopathological behavior compatible with the literature. Curative surgery is recommended in all cases.

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OBJECTIVE: To evaluate variables affecting the need for analgesia after ultrasound-guided percutaneous liver biopsy performed on an outpatient basis. MATERIALS AND METHODS: This was a retrospective analysis of 1,042 liver biopsies performed between 2012 and 2018. The data collected included the age and sex of the patient, as well as self-reported pain in the recovery room, the pain treatment used, the indication for the biopsy, and the lobe punctured. As per the protocol of our institution, physicians would re-evaluate patients with mild pain (1-3 on a visual analog scale), prescribe analgesics for those with moderate pain (4-6 on the visual analog scale), and prescribe opioids for those with severe pain (7-10 on the visual analog scale). RESULTS: The main indications for biopsy were related to diffuse disease (in 89.9%), including the follow-up of hepatitis C (in 47.0%) and suspicion of nonalcoholic steatohepatitis (in 38.0%). Pain requiring analgesia occurred in 8.0% of procedures. Of the 485 female patients, 51 (10.5%) needed analgesia, compared with 33 (5.9%) of the 557 male patients (p < 0.05). The need for analgesia did not differ in relation to patient age, the lobe punctured, or the indication for biopsy (nodular or diffuse disease). The analgesic most commonly used was dipyrone (in 75.9%), followed by paracetamol alone (16.4%) and their combination with opioids (7.6%). CONCLUSION: Ultrasound-guided percutaneous liver biopsy is safe and well tolerated. Postprocedural pain does not correlate with the lobe punctured, patient age, or the indication for biopsy and appears to affect more women than men.

OBJETIVO: Avaliar variáveis que afetam a necessidade de analgesia após biópsia hepática guiada por ultrassonografia. MATERIAIS E MÉTODOS: Análise retrospectiva de 1042 biópsias hepáticas realizadas entre 2012 e 2018. Os dados coletados incluíram dor detectada na sala de recuperação, analgesia utilizada, indicação, lobo puncionado, idade e sexo do paciente. O protocolo institucional indicava orientações e reavaliação para dor leve (1-3, segundo a escala visual analógica), analgésicos simples para dor moderada (4-6, segundo a escala visual analógica) e opioides para dor importante (7-10, segundo a escala visual analógica). RESULTADOS: As indicações foram principalmente doença difusa (89,9%), particularmente no seguimento de hepatite C (47,0%) e suspeita de esteato-hepatite não alcoólica (38,0%). Dor com necessidade de analgesia ocorreu em 8,0% dos procedimentos. Mulheres demandaram analgesia em 10,5% das vezes e homens demandaram em 5,9% (p < 0,05). Não houve diferença estatisticamente significante na necessidade de analgesia em relação a idade, lobo hepático puncionado ou indicação por doença nodular versus difusa. O analgésico mais utilizado foi dipirona (75,9%), seguido de paracetamol (16,4%) e associação com opioides (7,6%). CONCLUSÃO: Este é um procedimento seguro e bem tolerado. Dor pós-procedimento não se correlaciona com lateralidade da biópsia, idade ou doença nodular versus difusa e parece afetar mais mulheres que homens.

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Abstract Objective: To evaluate variables affecting the need for analgesia after ultrasound-guided percutaneous liver biopsy performed on an outpatient basis. Materials and Methods: This was a retrospective analysis of 1,042 liver biopsies performed between 2012 and 2018. The data collected included the age and sex of the patient, as well as self-reported pain in the recovery room, the pain treatment used, the indication for the biopsy, and the lobe punctured. As per the protocol of our institution, physicians would re-evaluate patients with mild pain (1-3 on a visual analog scale), prescribe analgesics for those with moderate pain (4-6 on the visual analog scale), and prescribe opioids for those with severe pain (7-10 on the visual analog scale). Results: The main indications for biopsy were related to diffuse disease (in 89.9%), including the follow-up of hepatitis C (in 47.0%) and suspicion of nonalcoholic steatohepatitis (in 38.0%). Pain requiring analgesia occurred in 8.0% of procedures. Of the 485 female patients, 51 (10.5%) needed analgesia, compared with 33 (5.9%) of the 557 male patients (p < 0.05). The need for analgesia did not differ in relation to patient age, the lobe punctured, or the indication for biopsy (nodular or diffuse disease). The analgesic most commonly used was dipyrone (in 75.9%), followed by paracetamol alone (16.4%) and their combination with opioids (7.6%). Conclusion: Ultrasound-guided percutaneous liver biopsy is safe and well tolerated. Postprocedural pain does not correlate with the lobe punctured, patient age, or the indication for biopsy and appears to affect more women than men.

Resumo Objetivo: Avaliar variáveis que afetam a necessidade de analgesia após biópsia hepática guiada por ultrassonografia. Materiais e Métodos: Análise retrospectiva de 1042 biópsias hepáticas realizadas entre 2012 e 2018. Os dados coletados incluíram dor detectada na sala de recuperação, analgesia utilizada, indicação, lobo puncionado, idade e sexo do paciente. O protocolo institucional indicava orientações e reavaliação para dor leve (1-3, segundo a escala visual analógica), analgésicos simples para dor moderada (4-6, segundo a escala visual analógica) e opioides para dor importante (7-10, segundo a escala visual analógica). Resultados: As indicações foram principalmente doença difusa (89,9%), particularmente no seguimento de hepatite C (47,0%) e suspeita de esteato-hepatite não alcoólica (38,0%). Dor com necessidade de analgesia ocorreu em 8,0% dos procedimentos. Mulheres demandaram analgesia em 10,5% das vezes e homens demandaram em 5,9% (p < 0,05). Não houve diferença estatisticamente significante na necessidade de analgesia em relação a idade, lobo hepático puncionado ou indicação por doença nodular versus difusa. O analgésico mais utilizado foi dipirona (75,9%), seguido de paracetamol (16,4%) e associação com opioides (7,6%). Conclusão: Este é um procedimento seguro e bem tolerado. Dor pós-procedimento não se correlaciona com lateralidade da biópsia, idade ou doença nodular versus difusa e parece afetar mais mulheres que homens.

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The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with ß-cyclodextrin (ß-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and ß-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the ß-CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the ß-cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/ß-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/ß-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.

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Passiflora alata or passion fruit is a native flowering plant from Amazon, geographically spread from Peru to Brazil. The plant has long been used in folks medicine for its pharmacological properties and is included in the Brazilian Pharmacopoeia since 1929. The aim of this study was to evaluate the potential cytotoxic and antitumor activities of Passiflora alata leaf extract (PaLE) in S180-tumor bearing mice. The percentage of cell proliferation inhibition (% CPI) and IC50 in relation to 4 tumor cell lines were determined in PC3, K-562, HepG2 and S180 cell lines using the MTT assay. PaLE showed a CPI > 75% and greater potency (IC50 < 30 µg/mL) against PC3 and S180 cell lines. PaLE showed antitumor activity in treatments intraperitoneally (36.75% and 44.99% at doses of 100 and 150 mg/kg/day, respectively). Toxicological changes were shown in the reduced body mass associated with reduced food consumption, increased spleen mass associated with histopathological increase in the white pulp of the spleen and increased number of total leukocytes with changes in the percentage relationship between lymphocytes and neutrophils. Our outcomes corroborate the conclusion that PaLE has antitumor activity in vitro and in vivo with low toxicity.

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The present study analyzes the importance of the inflammasome that involves the NLRP3 complex in the state of hypercytokinemia observed in patients with COVID-19, significantly increasing IL-1ß, IL18, IL-6, and TNF. Unfortunately, improving the immune response can sometimes worsen the outcome of the disease. Studies show that colchicine, among other actions, inhibits the assembly of NLRP3 complex that is responsible for generating the active form of Caspase-1 that will convert Pro-IL-1ß and Pro-IL-18 into their active forms. We suggest using colchicine, a class of drugs with low-cost, extensively tested, well-tolerated medicine as a complementary treatment for patients with COVID-19, in early stages of the disease based on knowledge of its immunomodulatory properties.

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Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 23 factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C).

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The enormous health and economic challenges precipitated by the 2019 coronavirus disease (COVID-19) pandemic are comparable or even greater than those associated with previous historical world crises. Alcohol use, especially drinking to cope with stress, is a concern, as an increase in its sales has been reported in some countries during the quarantine. This study aims to provide a better understanding of what to expect in terms of alcohol consumption, risk factors for excessive use, and its potential consequences during this pandemic based on previous experiences. We investigated how traumatic events related to alcohol consumption. Studies on mass traumatic events (i.e., terrorism as 9/11), epidemic outbreaks (i.e., severe acute respiratory syndrome [SARS] in 2003), economic crises (such as 2008's Great Recession), and COVID-19 were selected. The main keywords used to select the studies were alcohol use, drinking patterns, alcohol use disorders, and alcohol-related consequences. Previous studies reported increases in alcohol use associated with those events mediated, at least partially, by anxiety and depressive symptoms, and posttraumatic stress disorder (PTSD). Being male, young, and single also seems to be associated with a higher vulnerability to develop risky drinking behavior after those tragic events. The discussion of previous risk and protective factors can contribute to elaborate more specific public health policies to mitigate the impact of the current pandemic on people's mental health, especially alcohol-related problems.

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Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to produce micro/nanoparticles with a narrow size distribution and high encapsulation efficiency. The aim of this work was to produce cetyl palmitate SLNs using SCF to be loaded with praziquantel (PZQ) as an insoluble model drug. The mean particle size (nm), polydispersity index (PdI), zeta potential, and encapsulation efficiency (EE) were determined on the freshly prepared samples, which were also subject of Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), drug release profile, and in vitro cytotoxicity analyses. PZQ-SLN exhibited a mean size of ~25 nm, PdI ~ 0.5, zeta potential ~-28 mV, and EE 88.37%. The DSC analysis demonstrated that SCF reduced the crystallinity of cetyl palmitate and favored the loading of PZQ into the lipid matrices. No chemical interaction between the PZQ and cetyl palmitate was revealed by FTIR analysis, while the release or PZQ from SLN followed the Weibull model. PZQ-SLN showed low cytotoxicity against fibroblasts cell lines. This study demonstrates that SCF may be a suitable scale-up procedure for the production of SLN, which have shown to be an appropriate carrier for PZQ.

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