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Objective: To assess adherence to antihypertensive treatment in patients at a Family Health Strategy (FHS) unit. Methods: quantitative, transversal, and observational study with 131 hypertensive patients registered in the HIPERDIA program of an FHS located in the city of Lagarto, Sergipe, Brazil, through the analysis of medical records and the application of structured questionnaires. The assessment of the degree of adherence was carried out through the Brief Medication Questionnaire. Results: Factors related to poor adherence were illiteracy (PR: 0.61; 95%CI: 0.42 - 0.89), per capita family income < 1 minimum wage (PR: 0.51; 95%CI : 0.33 - 0.78) and high pharmacological complexity (PR: 0.66; 95%CI: 0.45 - 0.97), while only regular physical activity (PR: 2.64; 95%CI: 1.28 - 5.46) and a good quality of life (PR: 1.44; 95%CI: 1.02 - 2.04) remained positively associated with adherence. Conclusion: As these are modifiable factors, the simplification of the therapeutic scheme and the regular practice of physical activity are key points for increasing adherence to the treatment of systemic arterial hypertension in Primary Care. Objetivo: Avaliar a adesão ao tratamento anti-hipertensivo em pacientes de uma unidade de Estratégia Saúde da Família (ESF). Métodos: estudo quantitativo, transversal e observacional com 131 hipertensos cadastrados no programa HIPERDIA de uma ESF localizada na cidade de Lagarto, Sergipe, Brasil, por meio da análise de prontuários e aplicação de questionários estruturados. A avaliação do grau de adesão foi realizada por meio do Brief Medication Questionnaire. Resultados: Os fatores relacionados à baixa adesão foram analfabetismo (RP: 0,61; IC95%: 0,42 - 0,89), renda familiar per capita < 1 salário-mínimo (RP: 0,51; IC95%: 0,33 - 0,78) e alta complexidade farmacológica (RP: 0,66; IC95%: 0,45 - 0,97), mantendo-se apenas atividade física regular (RP: 2,64; IC95%: 1,28 - 5,46) e boa qualidade de vida (RP: 1,44; IC95%: 1,02 - 2,04) positivamente associadas à adesão. Conclusão: Por se tratar de fatores modificáveis, a simplificação do esquema terapêutico e a prática regular de atividade física são pontos fundamentais para aumentar a adesão ao tratamento da hipertensão arterial sistêmica na Atenção Básica.

A dependência causada pelo uso da cocaína representa um problema de saúde pública em vários países. Apesar do seu elevado potencial de causar dependência, ainda não há um protocolo clínico para o tratamento farmacológico. Entretanto, a partir de resultados positivos, alguns estudos clínicos já foram desenvolvidos com a finalidade de identificar terapias farmacológicas a fim de minimizar o desejo em consumir a substância. O tratamento farmacológico das adições consiste em psicotrópicos, que são medicamentos controlados que agem no Sistema Nervoso Central. Esses medicamentos contribuem para a redução dos sintomas de abstinência de drogas, além de sintomas de eventuais comorbidades psiquiátricas que o paciente venha a apresentar. Nesse sentido, a farmacoterapia age no tratamento da dependência química, complementando outras atividades que buscam melhorar a qualidade de vida dos pacientes. Este estudo teve como objetivo realizar um levantamento bibliográfico sobre o tratamento farmacológico da adicção de cocaína/crack levando-se em conta a análise da farmacoterapia diante de pacientes dependentes químicos. Para isso, foram utilizadas publicações disponibilizadas nas bases de dados da PUBMED, LILACS e BVS referentes ao período de 2012 a 2021. A partir da realização desta pesquisa, concluiu-se que apesar da grande incidência de usuários de drogas de abuso ainda não há um tratamento farmacológico definido para os indivíduos dependentes de cocaína/crack, sendo necessário, portanto, a realização de mais estudos sobre a temática com a finalidade de reduzir os sintomas da abstinência do uso da substância.

Schistosomiasis is a tropical disease spread in more than 54 countries affecting 261 million people around the world. This disease is considered neglected due to socioeconomic and biological factors combined with underreporting of cases. Different species of Schistosoma may be transmitted to its definitive host, the humans, however, in the Americas the Schistosoma mansoni is the predominant species. For the transmission to happen, direct contact of the host with water or food contaminated by S. mansoni eggs is required. After the infection, symptoms may appear, depending on the severity of the disease. The therapy is focused on the change of habits and the administration of the drug of first choice, praziquantel. New technological tools have been emerging aiming to optimize the treatment with praziquantel by improving its clinical efficacy with minimized side effects. This chapter addresses the free praziquantel and encapsulated in nanostructures with the aim to determine the effectiveness of these nanostructures through experimental data.

Cancer is a group of diseases characterized by the uncontrolled growth of cells. These cells invade organs and tissues by extension or direct dissemination and can spread to other regions of the body. Nanomedicine offers many possibilities to prevent the spread of cancer tissue and help cure the disease. In this work, solid lipid nanoparticles (SLN) were used to encapsulate perillyl alcohol (PA), a volatile monoterpene with proven anticancer activity. Encapsulation of PA into SLN (SLN-PA) is expected to promote controlled release, increase PA bioavailability, and impair the volatility of the monoterpene. SLN-PA prepared by high-shear homogenization showed average particle diameter around 254 nm, polydispersity index ~ 0.35, zeta potential ~ -14.7 mV, and encapsulation efficiency 84.6%. Scanning electron microscope analysis revealed a decrease in crystallinity, suggesting the encapsulation of PA in the SLN, confirming the spherical shape and the loading of the monoterpene in the SLN. In vitro cytotoxicity assays against murine fibroblasts (L929) showed that SLN-PA in both treated doses did not induce any cytotoxicity on non-tumoral cells. In vivo antitumor effect of the SLN-PA was evaluated in sarcoma 180-transplanted mice. The in vivo results demonstrated a significant tumor inhibition rate of 51.76 and 54.49% via intraperitoneal application of SLN-PA at doses of 100 and 200 mg/kg/day (p < 0.05), respective when compared to the negative control (dimethyl sulfoxide). Adverse side effects of SLN-PA were not noticed in the liver, the kidney, or spleen tissue. The developed SLN-PA can be considered as a safe approach for site-specific antitumor effect in vivo, reinterpreting new nanoparticles- based cancer therapy., This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

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 &gt, 75% and greater potency (IC50 &lt, 30 &micro, g/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.

Praziquantel (PZQ) is an anthelmintic drug, being the first choice for the treatment of schistosomiasis. Its high hydrophobic character and its low water solubility are the main limitations to the development of liquid formulations for the oral administration of the drug. The aim of this work was to develop Solid Lipid Nanoparticles (SLN) for the loading of PZQ for the treatment of S. mansoni infections. PZQ-SLN were produced by hot high shear homogenization. The obtained SLN exhibited a mean size of 300nm, with a polydispersity index of 0.20, zeta potential of-28mV and encapsulation efficiency of 92.31%. Thermal analysis demonstrated that the production process reduced the lipid crystallinity of the SLN matrices, which displayed a spherical morphology by scanning electron microscopy (SEM). The mathematical fitting of the release profile demonstrated that PZQ followed the Weibull model whereas PZQ-loaded SLN the Peppas model. PZQ-loaded SLN were more effective in inducing S. mansoni death than PZQ alone. The increased drug solubility did not exhibit toxicity against human fibroblast cell lines (L929). PZQ-loaded SLN demonstrated great parasiticidal properties, being an improved alternative to the classical treatment of schistosomiasis., The authors wish to acknowledge Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #443238/2014-6, #470388/2014-5). EBS wishes to acknowledge the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the projects M-ERA-NET0004/2015-PAIRED, co-financed by FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

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)., FCT -Fundação para a Ciência e a Tecnologia(UIDB/04469/2020), info:eu-repo/semantics/publishedVersion

The study aimed to evaluate cytotoxicity and antitumor activity of perillaldehyde 1,2-epoxide (PE), a p-menthane monoterpene derivative against four human tumor cell lines ovarian cancer (OVCAR-8), colon carcinoma (HCT-116), glioblastoma (SF-295) and leukemia (HL-60) using the colorimetric MTT assay. PE showed a high degree of inhibition of cell proliferation (GI = 95.66 to 99.71%) and IC50 16.14 μM (± 1.86), 23.61 μM (± 1.13), 21.99 μM (± 2.64) and, 9.70 μM (± 1.01) against tumor cells, respectively. Then, in vivo antitumor activity of the PE was assessed in sarcoma 180-bearing mice. Tumor growth inhibition rates were 33.4, 56.4 and 66.6% at doses of 100 and 200 mg/kg/day for the PE and 25 mg/kg/day for 5-FU intraperitoneal treatments, respectively. Toxicological effects related to the spleen, kidneys, liver, and hematological were investigated in mice submitted to treatment. Furthermore, histopathological analyses of these organs were absent of any morphological changes in the animals treated with PE. The viability of HL-60 cells was affected by perillaldehyde 1, 2-epoxide after an exposure period of 72 h when analyzed by trypan blue exclusion. PE reduced the number of viable cells associated with an increase in non-viable cells, which contributes to the increased number of dead cells in the morphological analysis. The incorporation of ethidium bromide/acridine orange, the treated cells suggests cytotoxicity via apoptosis and necrosis. So on the results, we conclude that PE presents cytotoxic and antitumoral activity through apoptotic and necrotic processes. Key words: Essential oils, p-menthanes, natural products, cytotoxicity, antitumor activity, sarcoma 180.

Punica granatum, specifically the fruit, has a long ethno medical history and is a phytochemical reservoir of great medicinal value. The phytochemistry and pharmacological actions of all P. granatum components suggest a wide range of clinical applications. The aim of the present study is to investigate the anticancer potential of aqueous extract of P. granatum (AEPG) in experimental models. The chemical composition of the AEPG was assessed by HPLC-DAD. In vivo antitumor activity was assessed in sarcoma 180 bearing mice. To evaluate the toxicological aspects related to the AEPG treatment, hematological, biochemical, histopathological and morphological analyses of treated animals were performed. Gallic acid, punicalagin α, punicalagin β, and ellagic acid were identified as the major phytochemical compounds of the extract. AEPG and 5-fluorouracil (5-FU) induced significant inhibition of tumor growth when compared with saline (p < 0.05). The percentage of apoptotic cells was significantly increased in 5-FU (p < 0.01) and AEPG treated groups (p < 0.01). No significant difference was observed between 5-FU and the three doses of AEPG. 5-FU induced toxic effects, such as decrease of body weight, splenic atrophy, and leukopenia, but these effects were not found in AEPG treated groups. The results provide evidence that AEPG exhibits comparable antitumor effects as 5-FU in a murine model, likely the result of increased apoptotic rate, but with no remarkable side effects presented by 5-FU. Key words: Cancer, chemotherapy, Punica granatum, sarcoma 180.

This work aimed to evaluate the cytotoxic potential against cancer cells of Passiflora genus plant species cultivated in Brazil and identify the mechanism of cytotoxicity induced by the most promising extract. Ethanolic extracts from the leaves of 14 Passiflora species were obtained by accelerated solvent extraction and in vitro cytotoxicity evaluated against cancer cell lines using MTT assay at a single concentration of 50 μg/ml. Additionally, the IC50 of the Passiflora alata (ELPA) leaf extracts was determined against both cancer (HCT-116, SF-295, OVACAR-8, and HL-60), and non-cancer cells (PBMC). The ELPA flavonoids were identified by HPLC-DAD and UHPLC-MS/MS. The morphological analyses, using light and fluorescence microscopy, and cell cycle and DNA fragmentation analysis, using flow cytometry, were evaluated to study the mechanism of cell death induced by ELPA in HL-60 cells. Among the Passiflora leaf extracts evaluated; ELPA stood out with high cytotoxic activity, followed by Passiflora capsularis and Passiflora quadrangularis with varying high and low cytotoxic activity. ELPA presented high cytotoxic potency in HL-60 (IC50 19.37 μg/ml), and without cytotoxicity against PBMC, suggesting selectivity for cancer cells. The cytotoxic activity of ELPA may well be linked to the presence of ten identified flavonoids. Cells treated with ELPA presented the hallmarks typical of apoptosis and necrosis, with cell cycle arrest in the G2/M phase. From among the studied species, ELPA presented greater cytotoxic activity, possibly a consequence of synergistic flavonoid action, which induces cell death by apoptosis and necrosis. Key words: Cancer, cytotoxicity, ethanolic extract, Passiflora, Passiflora alata.

In the previous study, we demonstrated that the essential oil from the leaves of Mentha x villosa (EOMV) shows antitumour activities. In the present paper, the effects of the combination of 5-fluorouracil (5-FU) with the EOMV were determined in mice transplanted with Sarcoma 180 tumour cells. Hematological and biochemical analyses, as well as morphological analyses of the tumour and the organs (liver, spleen and kidney) were performed in order to evaluate the toxicological aspects. The combination of the EOMV (50 and 100 mg/kg/day) with 5-FU (10 mg/kg/day) led to a higher tumour growth inhibition rate (58.9% and 65.7%, respectively) when compared with 5-FU alone at 10 mg/kg/day (30.2%). The combined use of 5-FU (10 mg/kg/day) with the EOMV (50 and 100 mg/kg/day) showed similar tumour growth inhibition rate to that of 5-FU alone at the highest dose (25 mg/kg/day) with less severe leukopenia. However, neither the enzymatic activity of transaminases nor the urea and creatinine levels were modified when compared with the 5-FU groups. These findings indicate that the EOMV may enhance the therapeutic effectiveness of chemotherapeutic drugs. Copyright © 2016 John Wiley & Sons, Ltd.

Nanomedicine manipulates materials at atomic, molecular, and supramolecular scale, with at least one dimension within the nanometer range, for biomedical applications. The resulting nanoparticles have been consistently shown beneficial effects for antifungal drugs delivery, overcoming the problems of low bioavailability and high toxicity of these drugs. Due to their unique features, namely the small mean particle size, nanoparticles contribute to the enhanced drug absorption and uptake by the target cells, potentiating the therapeutic drug effect. The topical route is desirable due to the adverse effects arising from oral administration. This review provides a comprehensive analysis of the use of nano compounds for the current treatment of topical fungal infections. A special emphasis is given to the employment of lipid nanoparticles, due to their recognized efficacy, versatility, and biocompatibility, attracting the major attention as novel topical nanocompounds used for the administration of antifungal drugs.

This work aimed to evaluate the cytotoxic potential against cancer cells of Passiflora genus plant species cultivated in Brazil and identify the mechanism of cytotoxicity induced by the most promising extract. Leaf extracts from 14 Passiflora (P.) species were obtained ASE and in vitro cytotoxicity evaluated against cancer cell lines using MTT assay at a single concentration of 50 μg/mL. Additionally, the IC50 of the P. alata (ELPA) leaf extracts was determined against both tumor (HCT-116, SF-295, OVACAR-8, and HL-60), and non-tumor cells (PBMC). The ELPA flavonoids were identified by HPLC-DAD and UHPLC-MS/MS. The morphological analyses used light and fluorescence microscopy, and cell cycle and DNA fragmentation analyses used flow cytometry to determine the mechanism of cell death induced by ELPA in HL-60. Among the Passiflora leaf extracts evaluated; ELPA stood out with high cytotoxic activity, followed by P. capsularis and P. quadrangulares with varying high and low cytotoxic activity. ELPA presented high cytotoxic potency in HL-60 (IC50 19.37 μg/mL), yet without cytotoxic activity against PBMC, suggesting selectivity for tumor cells. The cytotoxic activity of ELPA may well be linked to the presence of ten identified flavonoids. Cells treated with ELPA presented the hallmarks typical of apoptosis and necrosis, with cell cycle arrest in the G2/M phase. Conclusion: From among the studied species, ELPA presented greater cytotoxic activity, possibly a consequence of synergistic flavonoid action which induces cell death by apoptosis and necrosis.

Cancer is one of the leading causes of death around the world. Conventional cancer treatment is still associated with many side effects which make the treatment difficult to the acceptance by the patients. Nanotechnology came to help the human being to overcome and improve the cancer treatment. In the nanotechnology field, nanocomposite represents a new hope to enhance the cancer treatment, being by the use of nanocomposite in therapeutic or in diagnostic or even theranostic which would be the promising future of the medicine. It is not possible to address to nanocomposite for cancer treatment without mentioning the importance of the nanocomposite for the diagnostic system applications such as computed tomography and magnetic resonance imaging. More efforts should also be directed at scaled-up synthesis, long-term assessment of toxicity and establishment of regulatory protocols for diagnostic, nanotherapeutics, and nanotheranostics systems.

Objectives The aim of this study was to investigate the cytotoxic and antitumour effects of the essential oil from the leaves of Mentha x villosa (EOMV) and its main component (rotundifolone). Methods In-vitro cytotoxic activity of the EOMV and rotundifolone was determined on cultured tumour cells. In-vivo antitumour activity of the EOMV was assessed in sarcoma 180-bearing mice. Key findings The EOMV displayed cytotoxicity against human tumour cell lines, showing IC50 values in the range of 0.57–1.02 μg/ml in the HCT-116 and SF-295 cell lines, respectively. Rotundifolone showed weak cytotoxicity against HCT-116, SF-295 and OVCAR-8 cell lines (IC50 > 25.00 μg/ml). Tumour growth inhibition rates were 29.4–40.5% and 25.0–45.2% for the EOMV treatment by intraperitoneal (50–100 mg/kg/day) and oral (100–200 mg/kg/day) administration, respectively. The EOMV did not significantly affect body mass and macroscopy of the organs. Conclusions The EOMV possesses significant antitumour activity with low systemic toxicity, possibly due to the synergistic action of its minor constituents.

Recent studies have revealed the high cytotoxicity of p-menthane derivatives against human tumor cells. In this study, the substance perillaldehyde 8,9-epoxide, a p-menthane class derivative obtained from (S)-(−)-perillyl alcohol, was selected in order to assess antitumor activity against experimental sarcoma 180 tumors. Toxicological effects related to the liver, spleen, kidneys and hematology were evaluated in mice submitted to treatment. The tumor growth inhibition rate was 38.4%, 58.7%, 35.3%, 45.4% and 68.1% at doses of 100 and 200 mg/kg/day for perillaldehyde 8,9-epoxide, perillyl alcohol and 25 mg/kg/day for 5-FU intraperitoneal treatments, respectively. No toxicologically significant effect was found in liver and kidney parameters analyzed in Sarcoma 180-inoculated mice treated with perillaldehyde 8,9-epoxide. Histopathological analyses of the liver, spleen, and kidneys were free from any morphological changes in the organs of the animals treated with perillaldehyde 8,9-epoxide. In conclusion, the data suggest that perillaldehyde 8,9-epoxide possesses significant antitumor activity without systemic toxicity for the tested parameters. By comparison, there was no statistical difference for the antitumor activity between perillaldehyde 8,9-epoxide and perillyl alcohol.

Propolis is known for its biological properties and its preparations have been continuously investigated in an attempt to solve the problem of their standardization, an issue that limits the use of propolis in food and pharmaceutical industries. The aim of this study was to evaluate in vitro antioxidant, antimicrobial, antiparasitic, and cytotoxic effects of extracts of red, green, and brown propolis from different regions of Brazil, obtained by ethanolic and supercritical extraction methods. We found that propolis extracts obtained by both these methods showed concentration-dependent antioxidant activity. The extracts obtained by ethanolic extraction showed higher antioxidant activity than that shown by the extracts obtained by supercritical extraction. Ethanolic extracts of red propolis exhibited up to 98% of the maximum antioxidant activity at the highest extract concentration. Red propolis extracts obtained by ethanolic and supercritical methods showed the highest levels of antimicrobial activity against several bacteria. Most extracts demonstrated antimicrobial activity against Staphylococcus aureus. None of the extracts analyzed showed activity against Escherichia coli or Candida albicans. An inhibitory effect of all tested ethanolic extracts on the growth of Trypanosoma cruzi Y strain epimastigotes was observed in the first 24 h. However, after 96 h, a persistent inhibitory effect was detected only for red propolis samples. Only ethanolic extracts of red propolis samples R01Et.B2 and R02Et.B2 showed a cytotoxic effect against all four cancer cell lines tested (HL-60, HCT-116, OVCAR-8, and SF-295), indicating that red propolis extracts have great cytotoxic potential. The biological effects of ethanolic extracts of red propolis revealed in the present study suggest that red propolis can be a potential alternative therapeutic treatment against Chagas disease and some types of cancer, although high activity of red propolis in vitro needs to be confirmed by future in vivo investigations.