Production of new ent-hardwickiic acid derivatives by microbial transformation and their antifungal activity.

Ent-hardwickiic acid is the major compound of Copaifera pubiflora Benth oleoresin traditionally used in Brazilian folk medicine as an antimicrobial agent. Microbial transformation of ent-hardwickiic by Cunninghamella elegans ATCC 10028b resulted in two and five antifungal derivatives (four new ones) produced in the Czapek modified and Koch's K1 media, respectively. The derivatives were isolated and their structures were determined by spectral analysis, namely 1D/2D NMR and HR-ESIMS. All compounds were tested for cytotoxic and antifungal activities and they were not cytotoxic to the tested cell lines, but all derivatives showed fungicidal activity against Candida glabrata and Candida krusei, which have emerged as resistant to fluconazole. One of the yet unreported biotransformation products displayed the strongest activity with minimum fungicidal concentration values smaller than the other compounds, including fluconazole.

Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos / Seroprevalence of SARS-CoV-2 antibodies in patients with immune-mediated inflammatory diseases treated with biological and synthetic targeted therapies

INTRODUCCIÓN: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. OBJETIVO: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. MÉTODOS: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. RESULTADOS: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). CONCLUSIONES: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

BACKGROUND: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. AIM: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. METHODS: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. RESULTS: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). CONCLUSIONS: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.

Polyketide- and Terpenoid-Derived Metabolites Produced by a Marine-Derived Fungus, Peroneutypa sp.

Bioassay-guided investigation of the EtOAc-soluble extract of a culture of the marine-derived fungus Peroneutypa sp. M16 led to the isolation of seven new polyketide- and terpenoid-derived metabolites (1, 2, 4-8), along with known polyketides (3, 9-13). Structures of compounds 1, 2, and 4-8 were established by analysis of spectroscopic data. Absolute configurations of compounds 1, 2, 4, 6, 7, and 8 were determined by the comparison of experimental ECD spectra with calculated CD data. Compound 5 exhibited moderate antiplasmodial activity against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum.

Active music therapy in dementia: results from an open-label trial / Musicoterapia ativa na demência: resultados de um estudo aberto

OBJECTIVE: Cognitive, neuropsychiatric and functional deficits are core symptoms of dementia. Non- -pharmacological interventions, such as music therapy, when used in conjunction with pharmacological treatment, have the potential to alleviate these symptoms. The purpose of this preliminary study is to examine the active music therapy on cognition and neuropsychiatric symptoms in the elderly with mild and moderate dementia. METHODS: The initial sample consisted of outpatients with dementia (N = 15) and their family members or caregivers (N = 15). Two dyads did not complete the assessments before intervention and were excluded from the analysis. Thirteen females (N = 13) comprised the final sampled and were diagnosed with Alzheimer's disease (N = 10), vascular dementia (N = 2) and mixed dementia (N = 1), at mild (N = 11) and moderate (N = 2) dementia stage. Participants were enrolled in an open-label trial of active music therapy group, set to take place once weekly for 60 minutes over a period of 12 weeks. RESULTS: Participants experienced a slight improvement on cognition measured with Mini-Mental State Examination (p = 0.41), although without statistical significance and a statistically significant decrease in anxiety (p = 0.042) in post-intervention. There were no significant effects on quality of life and caregiver burden. CONCLUSIONS: Active music therapy is a promising intervention with good acceptance among participants. More studies with larger sample sizes are needed to confirm its effects and efficacy in cognitive and neuropsychiatric symptoms in dementia.

OBJETIVO: Distúrbios cognitivos, comportamentais e funcionais são sintomas nucleares na demência. Intervenções não farmacológicas, como a musicoterapia, quando usadas em conjunto com o tratamento farmacológico, têm o potencial de aliviar esses sintomas. O objetivo deste estudo preliminar é examinar a musicoterapia ativa na cognição e nos sintomas neuropsiquiátricos em idosos com demência leve e moderada. MÉTODOS: A amostra inicial foi composta por pacientes ambulatoriais com demência (N = 15) e seus familiares ou cuidadores (N = 15). Duas duplas não completaram as avaliações antes da intervenção e foram excluídas da análise. Treze mulheres (N = 13) compuseram a amostra final e foram diagnosticadas com doença de Alzheimer (N = 10), demência vascular (N = 2) e demência mista (N = 1), nos estágios leve (N = 11) e moderado (N = 2). Os participantes foram inscritos em um estudo aberto de grupo de musicoterapia ativa, programado para ocorrer uma vez por semana, com duração de 60 minutos, durante o período de 12 semanas. RESULTADOS: Os participantes experimentaram uma discreta melhora cognitiva medida pelo Miniexame do Estado Mental (p = 0.41), embora sem significância estatística, e uma diminuição estatisticamente significativa na ansiedade (p = 0.042) na pós-intervenção. Não houve efeitos significativos na qualidade de vida e sobrecarga do cuidador. CONCLUSÕES: A musicoterapia ativa é uma intervenção promissora, com boa aceitação entre os participantes. Mais estudos com amostras maiores são necessários para confirmar seus efeitos e eficácia em sintomas cognitivos e neuropsiquiátricos na demência.

Role of the antioxidant pathway in the healing of peptic ulcers induced by ischemia-reperfusion in male and female rats treated with Eugenia punicifolia.

Ischaemia and reperfusion (I/R)-induced gastrointestinal disorders are caused by free radicals, resulting in organ damage and functional disarrangement. This study aimed to investigate the healing effects of hydroalcoholic extracts from the leaves of Eugenia punicifolia (Kunth) DC. (HEEP) in male and female Wistar rats with I/R-induced peptic injuries, and the role of antioxidants in improving this response. After I/R-induced gastric and duodenal injuries, male and female [intact (INT) and ovariectomized (OVZ)] rats were orally treated with HEEP for 6 days. Biochemical analysis was used to determine the catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) activities, as well as malondialdehyde and reduced glutathione levels, to measure the gastric and duodenal healing process. Six days of HEEP treatment significantly decreased the I/R-induced gastric [male (73.68%), INT (52.83%), and OVZ (43.13%)] and duodenal damage [male (57.03%), INT (56.04%), and OVZ (54.83%)] in all groups. In OVZ rats, the healing effect of HEEP occurred because of the increased activity of SOD (2x) and CAT (1.16x) in the gastric mucosa. In the duodenal mucosa of INT rats, the extract reduced MPO (20.83%) activity. The 6-day HEEP treatment improved the healing of I/R-induced peptic ulcer injury, with the system acting differently in males and females. The antioxidant system is an important component of the HEEP activity during post-I/R mucosal recovery. This result revealed the importance of antioxidant compounds in minimizing the severity of I/R-related events.

Oil impact on the environment and aquatic organisms on the coasts of the states of Alagoas and Sergipe, Brazil - A preliminary evaluation.

The oil spill off the coast of the Brazilian Northeast region is one of the most significant global events regarding contamination and environmental impact in recent years. This work evaluates the effects of oil spills on the Northeast coasts between Alagoas and Sergipe states from October 2019 to January 2020. Analysis of some sampling points of seawater revealed the presence of Hg, Cd, Pb, and Cu in levels above the maximum concentration limits established by the Brazilian legislation. For water quality parameters, phosphorus, nitrite, and turbidity showed statistically different values. However, the chromatographic profiles of oil obtained from different beaches were quite similar. Seawater, fishes, and massunins (bivalve) presented the main polycyclic aromatic hydrocarbons: naphthalene, phenanthrene, fluoranthene, fluorene, and acenaphthalene. Therefore, the concentration of organic and inorganic contaminants determined in different environmental locations served as a subsidy to assess the effect of the preliminary oil spill on the Brazilian coast.

Brazilian southeast brown propolis: gas chromatography method development for its volatile oil analysis, its antimicrobial and leishmanicidal activities evaluation.

INTRODUCTION: Propolis is widely used in folk medicine, and many factors can affect its chemical composition, including abiotic factors that can influence plants and bees. Therefore, analytical methods are powerful techniques in the quality control of such products. OBJECTIVE: Develop and validate an analytical method for quantifying volatile compounds in Brazilian brown propolis, and evaluate its biological activities. METHODS: A gas chromatography flame ionisation detector (GC-FID) analytical method was validated, attending the parameters of international validation guidelines as ANVISA 2017 and ICH 2005, for quantification of compounds present in volatile oils from propolis. Evaluation of cytotoxic, antimicrobial, and leishmanicidal activities of the oil. RESULTS: The compounds 1,8-cineole, terpinen-4-ol, α-copaene, ß-caryophyllene, γ-muurolene, nerolidol, spathulenol, and γ-palmitolactone were isolated from the volatile fraction of a Brazilian brown propolis and used in the method validation. All the validation parameters of the method were satisfactory. The volatile fraction displayed a significant leishmanicidal activity, with half maximal inhibition concentration (IC50 ) = 21.3 µg/mL against amastigote forms and IC50 = 25.1 µg/mL against promastigote forms of Leishmania amazonensis. The oil also displayed an antibacterial effect by inhibiting the growth of Streptococcus mutans and Staphylococcus aureus at 25 µg/mL and 50 µg/mL, respectively, but it was not cytotoxic against AGP-01, He-La and CHO-K1cell lines, with IC50 > 100 µg/mL. CONCLUSION: The GC-FID method can be a useful tool in the quality control of propolis material. The southeast brown propolis showed a high chemical complexity in its volatile fraction, which displayed leishmanicidal activity and bactericidal activity.

Manual de monitorização do volume prescrito e infundido em terapia nutricional enteral / Manual for monitoring the volume prescribed and infused in enteral nutritional therapy

Esse Manual foi elaborado com a intenção de orientá-lo, quanto a importância do controle do prescrito e infundido na terapia nutricional enteral. Contém informações bem simples e seguras e que abrange toda a equipe multiprofissional.

Elaboração de um protocolo de terapia nutricional para pacientes queimados em um centro de tratamento de referência: Relato de experiência / Elaboration of a nutritional therapy protocol for burned patients in a reference treatment center: Experience report

OBJETIVO: Descrever a trajetória da construção de um protocolo de terapia nutricional para pacientes queimados em um centro de tratamento de referência. RELATO DE EXPERIÊNCIA: Para a construção do protocolo, foi inicialmente elaborado um fluxograma sistematizando as etapas da atenção nutricional ao paciente queimado. Feito isso, percebeu-se a necessidade de construir um instrumento facilitador para tomada de decisões relativas à conduta nutricional. Com esta finalidade, foram realizadas estimativas das necessidades energéticas do paciente queimado, com base nas equações preditivas encontradas na literatura e em indivíduo de referência eutrófico, conforme perfil nutricional predominante na unidade. Os resultados foram dispostos em tabela comparativa, estratificados por sexo, faixa etária e percentual de superfície corporal queimada (%SCQ) e analisados para definir a melhor forma de estimar as necessidades energéticas dos pacientes na prática clínica. Ainda com base nesta estimativa, nas recomendações encontradas na literatura científica e na dieta oral padrão da unidade, que fornece aproximadamente 2548Kcal/dia e 105g/dia de proteína, foram elaboradas sugestões sobre quando e como prescrever suplementos orais nutricionalmente completos, módulo de proteína, glutamina e indicar terapia nutricional enteral para estes pacientes, conforme a %SCQ (<20%, 20%-30%, >40%). CONCLUSÃO: A aplicação deste protocolo na prática clínica pode otimizar a terapia nutricional do paciente queimado, de forma a minimizar a deterioração e/ou recuperar o estado nutricional destes pacientes, contribuindo para melhores desfechos clínicos.

OBJECTIVE: To describe the trajectory of the construction of a nutritional therapy protocol for burn patients in a reference treatment center. EXPERIENCE REPORT: For the construction of the protocol, initially a flowchart was prepared, systematizing the stages of nutritional care with burned patients. That done, it was realized the need to build a facilitating instrument for making decisions regarding nutritional conduct. For this purpose, estimates of the burned patient's energy needs were performed, based on the predictive equations found in the literature and in eutrophic reference individual, according to the predominant nutritional profile in the unit. The results were displayed in a comparative chart, stratified by sex, age and total body surface area (%TBSA) and analyzed to define the best way to estimate the energy needs of patients in clinical practice. Based on this estimate, in the recommendations found in the scientific literature and the unit's standard oral diet which provides approximately 2548Kcal/day and 105g/day of protein, suggestions were made about when and how to prescribe nutritionally complete oral supplements, protein module, glutamine and provide enteral nutritional therapy to these patients, according to %TBSA (<20%, 20%, 30%, >40%). CONCLUSION: The application of this protocol in clinical practice can optimize a nutritional therapy of the burned patient, in order to minimize the deterioration and/or recover their nutritional status, contributing to the best clinical outcomes.

Pexiganan in Combination with Nisin to Control Polymicrobial Diabetic Foot Infections.

Diabetic foot ulcers (DFUs) are major complications of Diabetes mellitus being responsible for significant morbidity and mortality. DFUs frequently become chronically infected by a complex community of bacteria, including multidrug-resistant and biofilm-producing strains of Staphylococcus aureus and Pseudomonas aeruginosa. Diabetic foot infections (DFI) are often recalcitrant to conventional antibiotics and alternative treatment strategies are urgently needed. Antimicrobial Peptides (AMPs), such as pexiganan and nisin, have been increasingly investigated and reported as effective antimicrobial agents. Here, we evaluated the antibacterial potential of pexiganan and nisin used in combination (dual-AMP) to control the growth of planktonic and biofilm co-cultures of S. aureus and P. aeruginosa clinical strains, co-isolated from a DFU. A DFU collagen three-dimensional (3D) model was used to evaluate the distribution and efficacy of AMPs locally delivered into the model. The concentration of pexiganan required to inhibit and eradicate both planktonic and biofilm-based bacterial cells was substantially reduced when used in combination with nisin. Moreover, incorporation of both AMPs in a guar gum delivery system (dual-AMP biogel) did not affect the dual-AMP antimicrobial activity. Importantly, the application of the dual-AMP biogel resulted in the eradication of the S. aureus strain from the model. In conclusion, data suggest that the local application of the dual-AMPs biogel constitutes a potential complementary therapy for the treatment of infected DFU.

Chrysin Modulates Genes Related to Inflammation, Tissue Remodeling, and Cell Proliferation in the Gastric Ulcer Healing.

Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.

[Impact of preoperative oral nutrition therapy in patients undergoing surgery for colorectal cancer]. / Impacto de la terapia con inmunonutrición oral perioperatoria en pacientes sometidos a cirugía por cáncer colorrectal.

INTRODUCTION: Objective: the aim of the study is to evaluate the effect of preoperative and postoperative oral nutritional therapy in the prevention of malnutrition and postsurgical complications in colorectal cancer Patients and methods: patients who underwent oncological colorectal surgery between June 2014 and December 2015 are included. An evaluation of preoperative nutritional status is performed. Patients received IMPACT® (2/day) for 5-10 days previous surgery. In the postoperative period, patients received IMPACT®/24h from 3rd to 7th postoperative day. Patients with low rates of albumin (< 2.5) or postoperative ileus received parenteral nutrition. Data were analyzed with the statistical package SPSS 21.0. Results: two hundred and twenty colorectal cancer patients were included. Twenty-eight patients did not take the preoperative oral supplements. Following the intake of nutritional supplements, an improvement of prealbumin and transferrin was noticed. One hundred and twenty-one patients received oral nutrition and 41 received parenteral nutrition in the postoperative period. There were more postoperative complications among patients without preoperative nutritional supplements (50% vs 28.1%; p = 0.019), and hospital stay was higher 14.64 ± 11.86 vs 9.36 ± 5.5; p < 0.005). There were more complications among patients without postoperative oral nutritional supplements (24% vs 18.2%; p < 0.005), with more wound infection (1.9% vs 0.8%) and leaks (1.9% vs 0.8%). They also had a higher average stay (9.15 4.6 vs 7.57 2.5 days; p = 0.021). Conclusion: in our study, patients that received oral nutritional supplements prior and following colorectal surgery had a lower rate of complications and a shorter hospital stay.

INTRODUCCIÓN: Objetivo: evaluar el impacto de la inmunonutrición oral preoperatoria y postoperatoria en la prevención de la desnutrición y las complicaciones posquirúrgicas en cáncer colorrectal. Pacientes y método: estudio retrospectivo descriptivo observacional con una única cohorte. Se incluyeron todos los pacientes sometidos a cirugía por cáncer colorrectal desde junio de 2014 a diciembre de 2015, sin ningún criterio de exclusión. En un pequeño número de casos (28 pacientes) no se suministró suplementación nutricional oral y se consideran pérdidas del estudio. Se realizó una evaluación del estado nutricional preoperatorio (NSR-2002). Se pautó inmunonutrición durante los cinco o diez días previos a la intervención en función del resultado. En el postoperatorio, se añadió inmunonutrición al tercer día postoperatorio hasta el séptimo o hasta el alta hospitalaria. Los pacientes con albúmina < 2,5 g/dl o íleo prolongado recibieron nutrición parenteral. El análisis de los datos se realizó con el paquete estadístico SPSS 21.0. Resultados: se incluyeron 220 pacientes con cáncer colorrectal, de los cuales 28 fueron pérdidas del estudio. La suplementación preoperatoria mejoró significativamente las cifras de prealbúmina y transferrina al ingreso. En el postoperatorio recibieron nutrición enteral 121 pacientes y 41 nutrición parenteral. Los pacientes que no tomaron suplementos nutricionales preoperatorios tuvieron más complicaciones (50% vs. 28,1%; p = 0,019) y la estancia media fue superior (14,64 ± 11,86 vs. 9,36 ± 5,5; p < 0,005). Los pacientes que no tomaron suplementos en el postoperatorio tuvieron más complicaciones (24% vs. 18,2%; p < 0,005), destacando más infección de herida (1,9% vs. 0,8%) y más dehiscencia anastomótica (1,9% vs. 0,8%). Tuvieron también una estancia media superior (9,15 ± 4,6 vs. 7,57 ± 2,5 días; p = 0,021). Conclusión: la administración de suplementos nutricionales orales previo a la intervención y en el postoperatorio en la cirugía del cáncer colorrectal se ha asociado a menos complicaciones y estancia media.

Synthesis and Initial Biological Evaluation of Boron-Containing Prostate-Specific Membrane Antigen Ligands for Treatment of Prostate Cancer Using Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a therapeutic modality which has been used for the treatment of cancers, including brain and head and neck tumors. For effective treatment via BNCT, efficient and selective delivery of a high boron dose to cancer cells is needed. Prostate-specific membrane antigen (PSMA) is a target for prostate cancer imaging and drug delivery. In this study, we conjugated boronic acid or carborane functional groups to a well-established PSMA inhibitor scaffold to deliver boron to prostate cancer cells and prostate tumor xenograft models. Eight boron-containing PSMA inhibitors were synthesized. All of these compounds showed a strong binding affinity to PSMA in a competition radioligand binding assay (IC50 from 555.7 to 20.3 nM). Three selected compounds 1a, 1d, and 1f were administered to mice, and their in vivo blocking of 68Ga-PSMA-11 uptake was demonstrated through a positron emission tomography (PET) imaging and biodistribution experiment. Biodistribution analysis demonstrated boron uptake of 4-7 µg/g in 22Rv1 prostate xenograft tumors and similar tumor/muscle ratios compared to the ratio for the most commonly used BNCT compound, 4-borono-l-phenylalanine (BPA). Taken together, these data suggest a potential role for PSMA targeted BNCT agents in prostate cancer therapy following suitable optimization.

Byrsonima intermedia A. Juss partitions promote gastroprotection against peptic ulcers and improve healing through antioxidant and anti-inflammatory activities.

Byrsonima intermedia is a species of bush popularly used to treat gastrointestinal disorders, such as gastric ulcers, gastritis, and diarrhea. Previous studies have revealed that the methanolic crude extract of B. intermedia leaves has gastroprotective and healing properties. In this new study, we specifically investigated two purified partitions, ethyl acetate (EtOAc) and water (AcoAq), obtained from the crude extract to characterize the antiulcer effects of these two partitions and the mechanisms of action of this medicinal plant. The healing effects of these partitions on the gastric and duodenal mucosa were assessed after ischemia-reperfusion (I/R) or acetic acid-induced injury. The involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 1ß (IL-1ß), interleukin 10 (IL-10), and myeloperoxidase (MPO) activity and glutathione (GSH) levels were determined. The antibacterial activity against Helicobacter pylori was evaluated using microdilution methods. The phytochemical analysis of AcoAq revealed a predominance of oligomeric proanthocyanidins and galloyl quinic esters, whereas EtOAc was found to contain concentrated flavonoids. Both partitions led to a significant reduction in gastric lesions, but AcoAq was more effective than EtOAc with regard to anti-Helicobacter pylori activity in addition to protecting the gastric mucosa against ethanol, non-steroidal anti-inflammatory drugs (NSAIDs) and duodenal mucosal damage induced by cysteamine. Additionally, both partitions were associated with a significant increase in gastric and duodenal healing and increased gastric mucosal GSH content after damage induced by acetic acid. On the other hand, after 6 days of treatment, EtOAc was more effective than AcoAq in ameliorating gastric damage upon initiation of the gastric I/R, which was accompanied by a significant reduction in the activity of gastric mucosal MPO, IL 1-ß and TNF-alpha, as well as an elevation in IL-10 and GSH content. These results demonstrate that the oligomeric proanthocyanidins and galloyl quinic esters present in AcoAq were more effective in the prevention of gastric and duodenal ulcers due to the antioxidant effects of these compounds, whereas the flavonoids present in EtOAc were more effective due to their anti-inflammatory activity on the gastric and duodenal tissue. All these results confirm that the rich phytochemical diversity of B. intermedia contributes to the pharmacological actions of this medicinal plant on the gastrointestinal tract in addition to its activity against H. pylori.

Ensino das práticas integrativas e complementares na formação em enfermagem / Teaching of integrative and complementary practices in nursing graduation

Objetivo: relatar sobre o ensino das práticas integrativas e complementares na formação em Enfermagem. Método: trata-se de um estudo qualitativo, descritivo, tipo relato de experiência, acerca das atividades realizadas por 20 acadêmicos, um docente e um monitor do curso de Enfermagem de um centro universitário. Utilizou-se a ementa institucional do curso. Resultados: considerou-se que o percurso de ensinoaprendizagem das práticas complementares se realizou a partir de três frentes: o empoderamento teórico com aulas embasadas em metodologias ativas, críticas e reflexivas; a apresentação de seminários discursivos com temáticas referentes ao contexto e a realização das atividades práticas de auriculoacupuntura/auriculoterapia e Reiki. Conclusão: salienta-se a importância da Unidade Temática no curso de Enfermagem do centro universitário, pois a utilização das práticas integrativas e complementares na assistência à saúde possibilita, aos estudantes, perceber o ser humano na sua totalidade. Sugere-se, dessa forma, que a temática deve ser implantada em outras instituições de ensino, bem como incorporada desde o início da formação dos estudantes, pois esses conhecimentos e práticas contribuem, de forma coadjuvante, para os cuidados aos clientes, assistindo-os de forma holística.(AU)

Potential of two delivery systems for nisin topical application to dental plaque biofilms in dogs.

BACKGROUND: Periodontal disease (PD) is caused by the development of a microbial biofilm (dental plaque) in the periodontium, affecting approximately 80% of dogs. Several bacterial species present in the canine oral cavity can be implicated in the development of this disease, including Enterococcus spp. To decrease antibiotic administration, a possible control strategy for dog's enterococcal PD may involve the use of the antimicrobial peptide (AMP) nisin. Nisin's inhibitory activity was evaluated against a collection of previously characterized enterococci obtained from the oral cavity of dogs with PD (n = 20), as well as the potential of a guar-gum gel and a veterinary toothpaste as topical delivery systems for this AMP. The Minimum Inhibitory (MIC) and Bactericidal Concentrations (MBC) and the Minimum Biofilm Eradication (MBEC) and Inhibitory Concentrations (MBIC) were determined for nisin and for the supplemented guar-gum gel. For the supplemented veterinary toothpaste an agar-well diffusion assay was used to evaluate its inhibitory potential. RESULTS: Nisin was effective against all isolates. Independently of being or not incorporated in the guar-gum gel, its inhibitory activity on biofilms was higher, with MBIC (12.46 ± 5.16 and 13.60 ± 4.31 µg/mL, respectively) and MBEC values (21.87 ± 11.33 and 42.34 ± 16.61 µg/mL) being lower than MIC (24.61 ± 4.64 and 14.90 ± 4.10 µg/mL) and MBC (63.09 ± 13.22 and 66.63 ± 19.55 µg/mL) values. The supplemented toothpaste was also effective, showing inhibitory activity against 95% of the isolates. CONCLUSIONS: The inhibitory ability of nisin when incorporated in the two delivery systems was maintained or increased, demonstrating the potential of these supplemented vehicles to be applied to PD control in dogs.

Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats.

AIM: To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia (HEEP) leaves on gastric ulcer healing. METHODS: In this rat study involving males, intact (cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity. RESULTS: Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males (52.44%), intact females (85.22%), and ovariectomized females (65.47%), confirming that HEEP accelerates the healing of acetic acid-induced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor (intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2 (intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed. CONCLUSION: In gastric ulcers, HEEP-induced healing (modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.

Percepção dos acompanhantes das crianças hospitalizadas acerca do brinquedo terapêutico / Perception of the hospitalized child's companion in relation to therapeutic toys

Objetivo: identificar a percepção dos acompanhantes das crianças hospitalizadas com relação às atividades lúdicas. Método: trata-se de estudo qualitativo, de campo, descrito e exploratório, com dez acompanhantes, uutilizando-se a ferramenta Brinquedo terapêutico. Coletaram-se os dados por meio de entrevista com roteiro semiestruturado. Empregou-se a técnica de Análise de Conteúdo na modalidade Análise Categorial para análise dos dados. Resultados: elegeram-se, a partir da leitura e releitura das entrevistas, quatro categorias: << A brinquedoteca como auxílio no tratamento pediátrico >>, << Utilização do Brinquedo Terapêutico na realização dos procedimentos >>; << O brinquedo terapêutico como suporte da assistência de Enfermagem >>, << O brinquedo e a aproximação entre o profissional e a criança >>. Conclusão: considerou-se primordial que os profissionais atuantes na Pediatria desenvolvam estratégias para a utilização do brinquedo terapêutico, melhorando a assistência oferecida e como contribuição, proporcionando o atendimento mais humano e qualificado na área.(AU)

Comparative study of cytotoxicity and genotoxicity of commercial Jeffamines® and polyethylenimine in CHO-K1 cells.

Jeffamines® are a family of polymers containing primary amine groups attached to the extremities of polyether backbone which can be used as biomaterials. They have been used in combination with polyethylenimine (PEI) to improve biocompatibility in drug and gene delivery systems. Despite these facts, very few studies have been done on cytotoxicity and genotoxicity of pure Jeffamines® or compared with PEI. The present study aimed to evaluate and compare the cytotoxic and genotoxic effects of Jeffamines® and PEI in CHO-K1 cells. Specifically, polypropylene oxide 2000 (PPO 2000, Jeffamine® D series), polyethylene oxide 1900 (PEO 1900, Jeffamine® ED series), branched 25 kDa PEI, and linear 20 kDa PEI were evaluated at different concentrations. Cell viability and proliferation were assessed by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and 5-bromo-2'-deoxyuridine (BrdU) assays, respectively. Genotoxicity was evaluated using single cell gel electrophoresis assay and the cytokinesis-blocked micronucleus assay. PPO 2000 was the most cytotoxic Jeffamine® , whereas PEO 1900 did not caused significant cell death at any tested concentration. Branched PEI was more cytotoxic than linear PEI (LPEI) and both were more cytotoxic than Jeffamines® . Only PPO 2000 induced DNA damage when evaluated in comet assay probably due to its cytotoxicity. PPO 2000, PEO 1900, and PEI did not increase the frequency of micronuclei when tested at sub-cytotoxic concentrations. This work provides new insights about biocompatibility of Jeffamines® and PEI and suggests the genotoxicological safety for further investigations of PEO 1900 in drug and gene delivery systems. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 742-750, 2018.

Therapeutic treatment with scFv-PLGA nanoparticles decreases pulmonary fungal load in a murine model of paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is a systemic mycosis with lymphatic dissemination that is caused by Paracoccidioides species. Treatment of PCM consists of chemotherapeutics such as itraconazole, trimethoprim, sulfamethoxazole or amphotericin B. However, several studies are aiming to develop therapeutic alternatives for the treatment of fungal infection using new molecules as adjuvants. The single-chain variable fragments (scFv) from an antibody that mimics the main fungal component incorporated within poly(lactide-co-glycolic) acid (PLGA) nanoparticles helped treat the fungal disease. After expressing the scFv in Picchia pastoris (P. pastoris), the recombinant molecules were coupled with PLGA, and the BALB/c mice were immunized before or after infection with yeast Paracoccidioides brasiliensis (P. brasiliensis). Our results showed decreased disease progression and decreased fungal burden. Taken together, our results showed an increased of IFN-γ and IL-12 cytokine production and an increased number of macrophages and dendritic cells in the pulmonary tissue of BALB/c mice treated with a high concentration of our molecule. Our data further confirm that the scFv plays an important role in the treatment of experimental PCM.