A Second Wind for Inorganic APIs: Leishmanicidal and Antileukemic Activity of Hydrated Bismuth Oxide Nanoparticles.

American cutaneous leishmaniasis is a disease caused by protozoa of the genus Leishmania. Currently, meglumine antimoniate is the first-choice treatment for the disease. The limited efficacy and high toxicity of the drug results in the necessity to search for new active principles. Nanotechnology is gaining importance in the field, since it can provide better efficacy and lower toxicity of the drugs. The present study aimed to synthesize, characterize, and evaluate the in vitro leishmanicidal and antileukemic activity of bismuth nanoparticles (BiNPs). Promastigotes and amastigotes of L. (V.) guyanensis and L. (L.) amazonensis were exposed to BiNPs. The efficacy of the nanoparticles was determined by measurement of the parasite viability and the percentage of infected cells, while the cytotoxicity was characterized by the colorimetry. BiNPs did not induce cytotoxicity in murine peritoneal macrophages and showed better efficacy in inhibiting promastigotes (IC50 < 0.46 nM) and amastigotes of L. (L.) amazonensis. This is the first report on the leishmanicidal activity of Bi-based materials against L. (V.) guayanensis. BiNPs demonstrated significant cytotoxic activity against K562 and HL60 cells at all evaluated concentrations. While the nanoparticles also showed some cytotoxicity towards non-cancerous Vero cells, the effect was much lower compared to that on cancer cells. Treatment with BiNPs also had a significant effect on inhibiting and reducing colony formation in HL60 cells. These results indicate that bismuth nanoparticles have the potential for an inhibitory effect on the clonal expansion of cancer cells.

Immunomodulatory and Anticancer Effects of Fridericia chica Extract-Loaded Nanocapsules in Myeloid Leukemia.

Nanocapsules provide selective delivery and increase the bioavailability of bioactive compounds. In this study, we examined the anticancer and immunomodulatory potential of Fridericia chica (crajiru) extract encapsulated in nanocapsules targeting myeloid leukemias. Nanocapsules containing crajiru (nanocapsules-CRJ) were prepared via interfacial polymer deposition and solvent displacement. Size and polydispersity were measured by dynamic light scattering. Biological assays were performed on leukemia cell lines HL60 and K562 and on non-cancerous Vero cells and human PBMC. The anticancer activity was evaluated using cytotoxicity and clonogenic assays, while the immunomodulatory activity was evaluated by measuring the levels of pro- and anti-inflammatory cytokines in PBMC supernatants treated with concentrations of nanocapsules-CRJ. Nanocapsules-CRJ exhibited significant cytotoxic activity against HL60 and K562 cells at concentrations ranging from 0.75 to 50 µg/mL, with the greatest reductions in cell viability observed at 50 µg/mL (p < 0.001 for HL60; p < 0.01 for K562), while not affecting non-cancerous Vero cells and human PBMCs. At concentrations of 25 µg/mL and 50 µg/mL, nanocapsules-CRJ reduced the formation of HL60 and K562 colonies by more than 90% (p < 0.0001). Additionally, at a concentration of 12 µg/mL, nanocapsules-CRJ induced the production of the cytokines IL-6 (p = 0.0002), IL-10 (p = 0.0005), IL-12 (p = 0.001), and TNF-α (p = 0.005), indicating their immunomodulatory potential. These findings suggest that nanocapsules-CRJ hold promise as a potential therapeutic agent with both cytotoxic and immunomodulatory properties.

Pharmacological assessment of the antineoplastic and immunomodulatory properties of a new spiroindolone derivative (7',8'-Dimethoxy-1',3'-dimethyl-1,2,3',4'-tetrahydrospiro[indole-3,5'-pyrazolo[3,4-c]isoquinolin]-2-one) in chronic myeloid leukemia.

The discovery and development of effective novel compounds is paramount in oncology for improving cancer therapy. In this study, we developed a new derivative of spiroindolone (7',8'-Dimethoxy-1',3'-dimethyl-1,2,3',4'-tetrahydrospiro[indole-3,5'- pyrazolo[3,4-c]isoquinolin]-2-one) and evaluated its anticancer- and immunomodulatory potential in a vitro model of chronic leukemia. We utilized the chronic leukemia cell line K562, as well as non-cancerous peripheral blood mononuclear cells (PBMC) and Vero cells (kidney epithelium of Cercopithecus aethiops). We assessed the cytotoxicity of the compound using the MTT assay, and performed cell cycle assays to determine its impact on different stages of the cell cycle. To evaluate its antineoplastic activity, we conducted a colony formation test to measure the effect of the compound on the clonal growth of cancer cells. Furthermore, we evaluated the immunomodulatory activity of the compound by measuring the levels of pro and anti-inflammatory cytokines. The study findings demonstrate that the spiroindolone-derived compound exerted noteworthy cytotoxic effects against K562 cells, with an IC50 value of 25.27 µg/mL. Additionally, it was observed that the compound inhibited the clonal proliferation of K562 cells while displaying minimal toxicity to normal cells. The compound exhibited its antiproliferative activity by inducing G2/M cell cycle arrest, preventing the entry of K562 cells into mitosis. Notably, the compound demonstrated an immunomodulatory effect by upregulating the production of cytokines IL-6 and IL-12/23p40. In conclusion, the spiroindolone-derived compound evaluated in this study has demonstrated significant potential as a therapeutic agent for the treatment of chronic myeloid leukemia. Further investigations are warranted to explore its clinical applications.

Cytotoxic and immunomodulatory potential of a novel [2-(4-(2,5-dimethyl-1H-pyrrol-1-yl)-1H-pyrazol-3-yl)pyridine] in myeloid leukemia.

Cancer ranks among the leading causes of mortality worldwide. However, the efficacy of commercially available anticancer drugs is compromised by the emerging challenge of drug resistance. This study aimed to investigate the anticancer and immunomodulatory potential of a recently developed a novel [2-(4-(2,5-dimethyl-1 H-pyrrol-1-yl)- 1 H-pyrazol-3-yl) pyridine]. The cytotoxic potential of the compound was assessed using the MTT assay on both cancerous HL60 (acute myeloid leukemia) and K562 (chronic myeloid leukemia) cell lines, as well as non-cancerous Vero cells and human peripheral blood mononuclear cells (PBMCs). A clonogenic assay was employed to evaluate the anticancer efficacy of the compound, while flow cytometry was utilized to investigate its effect on cell cycle arrest. Furthermore, the immunomodulatory potential of the compound was assessed by quantifying inflammatory and anti-inflammatory biomarkers in the supernatant of PBMCs previously treated with the compound. Our study revealed that the novel pyridine ensemble exhibits selective cytotoxicity against HL60 (IC50 = 25.93 µg/mL) and K562 (IC50 = 10.42 µg/mL) cell lines, while displaying no significant cytotoxic effect on non-cancerous cells. In addition, the compound induced a decrease of 18% and 19% in the overall activity of COX-1 and COX-2, respectively. Concurrently, it upregulated the expression of cytokines including IL4, IL6, IL10, and IL12/23p40, while downregulating INFγ expression. These findings suggest that the compound has the potential to serve as a promising candidate for the treatment of acute and chronic myeloid leukemias due to its effective antiproliferative and immunomodulatory activities, without causing cytotoxicity in non-cancerous cells.

Phenolic Composition, Wound Healing, Antinociceptive, and Anticancer Effects of Caralluma europaea Extracts.

Caralluma europaea (Guss.) is an important medicinal plant widely used in Morocco for various traditional purposes. Our work aimed to evaluate the phenolic composition, wound healing, antinociceptive, and anticancer activities of C. europaea extracts. Moreover, this study assessed the beneficial effect of C. europaea phytocompounds on the TRADD, cyclooxegenase-2, Wnt/ß-catenin, and tyrosine kinase signaling pathways. The wound healing effect of C. europaea formulations against skin burn was evaluated for 21 days. The cytotoxic effect of the C. europaea extracts was evaluated against human leukemic (K562 and HL60) and liver cancer cell lines (Huh-7) using the MTT test. All the phytoconstituents identified by UHPLC in the polyphenols were docked for their inhibitory power on protein casein kinase-1, glycogen synthase kinase-3-ß, cyclooxegenase-2, tyrosine kinase, and TRADD. Luteolin and kaempferol are the main compounds identified in C. europaea polyphenols. The group treated with polyphenols showed the greatest wound contractions and all tested extracts presented a significant antinociceptive effect. Polyphenols showed a remarkable antitumoral activity against the K562, HL60 and Huh-7 cell lines. Saponins exerted an important cytotoxic effect against the Huh-7 cell line, whereas no cytotoxicity was observed for the hydroethanolic and flavonoids extracts. Hesperetin and trimethoxyflavone presented the highest docking G-score on tyrosine kinase and cyclooxygenase, respectively.

Antileukemic, Antioxidant, Anti-Inflammatory and Healing Activities Induced by a Polyphenol-Enriched Fraction Extracted from Leaves of Myrtus communis L.

Natural products have offered a number of exciting approaches in cancer treatment over the years. In this study, we investigated the prophylactic and therapeutic effects of the polyphenol-enriched fraction extracted from Myrtus communis (PEMC) on acute and chronic leukemia. According to the UHPLC-MSn, the fraction is rich in flavonoids. Protective activity of the PEMC was assessed by evaluating the antioxidant, anti-inflammatory, wound healing, and hemolysis potential in a series of in vivo and in vitro assays, while the therapeutic approach consisted of the evaluation of cytotoxic activity of the PEMC against HL60 and K562 leukemia cell lines. Safety of the fraction was also evaluated on a non-cancerous Vero cell line and by an acute toxicity test performed in mice. The PEMC demonstrated a significant anti-inflammatory and healing potential. The activities found at the dose of 100 mg/kg were better than those observed using a reference drug. The PEMC demonstrated a significant antioxidant effect and a specific cytotoxicity towards HL60 (IC50 = 19.87 µM) and K562 (IC50 = 29.64 µM) cell lines being non-toxic to the Vero cell line. No hemolytic activity was observed in vitro and no toxicity effect was found in mice. Thus, the PEMC has a pharmacological potential as both preventive and therapeutic agent. However, further research is necessary to propose its mechanism of action.

The Relationship between Carcass Condemnations and Tail Lesion in Swine Considering Different Production Systems and Tail Lengths.

Tail biting has been recognised as an intractable problem in pig production. This study aims to evaluate tail lesion occurrence in slaughtered pigs and explore the relationship between carcass condemnations and tail lesion considering different production systems and tail lengths and to evaluate the importance of creating a detailed tail score classification that includes scarred lesions. Data on a total of 9189 pigs from 73 batches with different tail lengths (undocked; docked mid-length; fully docked) and from distinct production systems (conventional; conventional antibiotic-free and organic) were collected at a Spanish abattoir. Batches with higher tail lesion scores presented a significantly higher chance of total condemnation and total condemnation due to pyaemia, being even more associated with scarring score. The within-batches probability for local condemnations and local condemnation due to abscesses increased significantly with higher scarring scores. Regarding tail length, docked at mid-length and undocked carcasses presented significantly higher odds to be condemned due to abscess. Organic farms showed a higher probability of total condemnations. This research highlights the importance of tail lesions on carcass condemnations that may also be influenced by docking and type of production. Results suggest that scarring score should be included in the tail surveillance program.

Neither see, nor look: viewing! On adolescents' exhibition on social media / Nem ver, nem olhar: visualizar! sobre a exibição dos adolescentes nas redes sociais

RESUMO: Este trabalho discute o fenômeno da exibição dos adolescentes nas redes sociais. Iniciamos interrogando o enfraquecimento do Outro parental e os impasses decorrentes dos avanços da virtualidade na contemporaneidade. Recuperamos o debate sobre o narcisismo na adolescência, apresentando o "dar-se a ver" e a "exibição" como mecanismos distintos em relação ao olhar do Outro da cultura. Seguindo as proposições de Lacan sobre o instante de ver e a esquize do olho e do olhar, concluímos que o visualizar é uma operação dominante no ato de exibição, levando os jovens à repetição e não à estabilização no campo do Outro.

Abstract: This paper discusses the phenomenon of adolescent exhibition in social media. We started by questioning the weakening of the parental Other and the impasses arising from the advances of virtuality in contemporary times. We rescue the debate about narcissism in adolescence, presenting the "offer of oneself to the gaze" and the "exhibition" as distinct mechanisms in relation to the Other's look in the culture. According to Lacan's propositions about the moment of seeing, as well as the eye and gaze's "schize", the research concludes that viewing is a dominant operation within the act of exhibiting, which leads to repetition and not stabilization of adolescents in the field of the Other.

Avaliação de potenciais interações medicamentosas em pacientes da unidade de terapia intensiva de um hospital universitário / Evaluation of potential drug interactions in patients of the intensive therapy unit of university hospital

Introdução: entende-se por interação medicamentosa a ação de um medicamento, alimento ou qualquer substância química sobre o efeito de outro medicamento gerando uma resposta farmacológica ou clínica. Associações de fármacos no tratamento de doenças crônicas são muito comuns, principalmente em pacientes de unidade de terapia intensiva, no entanto, podem causar algumas interações medicamentosas, as quais podem ser responsáveis por insucesso terapêutico e aumento dos custos hospitalares. Objetivo: analisar a ocorrência e o perfil de potenciais interações medicamentosas em pacientes da UTI do Hospital Universitário Alcides Carneiro em Campina Grande-PB. Metodologia: realizou-se um estudo transversal descritivo, com abordagem quantitativa e qualitativa, a partir de dados coletados de prescrições da UTI entre janeiro e junho de 2017, utilizando um formulário específico. Para identificação das potenciais interações utilizou-se o Drug-Reax System do software Micromedex® Health Series. Resultados: dentre as 109 prescrições avaliadas, 69,7% apresentaram alguma interação, totalizando 244 potenciais interações. Foram detectados em média 6,9 medicamentos/prescrição. A maioria das interações apresentou mecanismo de ação farmacodinâmico, grau de severidade maior, razoável documentação e início de ação não especificado. Todas as prescrições com mais de 10 fármacos apresentaram algum tipo de interação. Conclusão: o surgimento de interações em UTI possui alta prevalência, mas as associações são justificadas pelo seu risco/benefício, por isso devem ser avaliadas e monitoradas pelo farmacêutico e a equipe de saúde, com intuito de reduzir falhas terapêuticas e risco ao paciente, aperfeiçoando assim o manejo clínico.

Introduction: drug interaction is the action of a drug, food or any chemical substance on the effect of another drug generating a pharmacological or clinical response. Associations of drugs in the treatment of chronic diseases are very common, especially in intensive care unit patients, however, they may cause some drug interactions, which are responsible for therapeutic failure and increased hospital costs. Objective: analyzing the occurrence and the profile of potential drug interactions in patients of the Hospital Universitário Alcides Carneiro in Campina Grande-PB. Methodology: a descriptive cross-sectional study was conducted with a quantitative and qualitative approach, based on data collected from ICU medical prescriptions between January and June 2017, using a specific form. The Drug-Reax System of the Micromedex® Health Series software was used to identify the potential interactions. Results: among the 109 prescriptions evaluated, 69.72% presented some interaction, totaling 244 potential interactions. 6.91 medications/prescription were detected on average. The majority of the interactions presented pharmacodynamic mechanism of action, greater degree of severity, reasonable documentation and unspecified onset of action. All prescriptions with more than 10 drugs presented some type of interaction. Conclusion: the emergence of interactions in ICUs has high prevalence, but the associations are justified by their risk / benefit, so they should be evaluated and monitored by the pharmacist and the health team, in order to reduce the emergence of potential interactions that lead to therapeutic failure and risk to the patient, thus improving clinical management

Sensibilidade dos S. aureus aos betalactâmicos e glicopeptídeos ("Estudo in vitro") / Sensitivity of S. aureus to beta-lactam and glycopeptide. ("In vitro")

Staphylococcus aureus podem ser encontrados na microbiota normal da pele e das mucosas dos seres humanos. Apresenta fácil disseminação e uma elevada patogenicidade através de vários mecanismos de ação. São agentes de infecções tanto do tipo superficial como profundo. Eles provocam, em muitos casos, a septicemia e a morte do paciente. Objetivo: O uso indiscriminado de antibióticos tem levado à criação de microrganismos resistentes, sendo o objetivo deste trabalho o de comparar in vitro o grau de efetividade de antibióticos betalactâmicos e glicopeptídeo na inibição de Staphylococcos aureus, comparando sua efetividade em feridas cirúrgicas infectadas. Métodos: Foram utilizadas culturas puras de Staphylococcus aureus. Na realização da parte experimental, foram selecionados os antimicrobianos amoxilina, oxacilina, cefepime, cefotaxima, cefalotina 39 e vancomicina. Conclusão: As cepas-teste mostraram-se resistentes à amoxicilina e sensível a todos os outros antimicrobianos testados.

Staphylococcus aureus can be found in normal flora of the skin and mucous membranes of humans. It features easy dissemination and high pathogenicity through multiple mechanisms of action. The agents of infections of both superficial and deep type. They often lead to septicemia and death of the patient. Objective: The indiscriminate use of antibiotics has led to the creation of resistant microorganisms, with the aim of this study was to compare in vitro the degree of effectiveness of beta-lactam antibiotics and glycopeptide in the inhibition of Staphylococcus aureus by comparing its effectiveness in surgical wound infection. Methods: We used pure cultures of Staphylococcus aureus. In the conduct of the trial were selected antimicrobials amoxicillin, oxacillin, cefepime, cefotaxime, cephalothin and vancomycin. Conclusion: The test strains were resistant to amoxicillin and susceptible to all antimicrobials tested.

Nutriçäo parenteral prolongada: aspectos gerais e cuidados de enfermagem / Parenteral nutrition: general aspects and nursing care

Apresenta-se um breve estudo sobre NPP e a responsabilidade da enfermeira na assistência ao paciente.

Parada cardio-respiratória: assistência de enfermagem / Cardio-respiratory arrest: nursing assistance

É analisada uma emergência comum em Unidades de Terapia Intensiva (UTI), a parada cardio-respiratória. Enfatiza-se o valor da atuaçäo da equipe de enfermagem, antecipando condutas e medidas para que a assistência ao paciente se efetue em tempo hábil. Pretende-se, com base em alguns anos de experiência, contribuir para a melhoria da assistência de enfermagem em UTI.