21­Benzylidene digoxin, a novel digoxin hemi-synthetic derivative, presents an anti-inflammatory activity through inhibition of edema, tumour necrosis factor alpha production, inducible nitric oxide synthase expression and leucocyte migration.

Recent findings have demonstrated new therapeutic functions of cardiotonic steroids, a process that is termed drug repositioning. Despite the confirmed anti-inflammatory effects of cardiotonic steroids, their clinical use has been discouraged due to toxicity related to inhibition of the Na+/K+ ATPase. A novel synthetic compound derived from digoxin, 21­benzylidene digoxin (21­BD), does not inhibit this enzyme. Herein, we evaluated the anti-inflammatory and antinociceptive effects and acute toxicity of 21­BD. Murine (Swiss mice) models of paw oedema induced by carrageenan, acetic acid-induced abdominal writhing, and formalin and acute toxicity tests were used. Oral administration of 21­BD (0.3 mg/kg) showed a significant and prolonged inhibition of paw oedema. Histological analysis demonstrated a reduction in inflammatory cells and expression of inducible nitric oxide synthase (iNOS) in footpads 6 h after administration of carrageenan. 21­BD (0.3 mg/kg) also reduced the levels of tumour necrosis factor (TNF)-α 2 and 4 h after carrageenan. 21­BD demonstrated antinociceptive activity, inhibiting abdominal writhes at all tested doses. However, in the formalin test, 21­BD did not present antinociceptive activity. In the acute toxicity test, 21­BD did not cause symptoms of toxicity or mortality. The present study demonstrated, for the first time, that 21­BD is safe and exhibits a marked anti-inflammatory activity in acute local inflammation. This effect might be a consequence of its ability to inhibit the release of the PMN leucocyte-derived mediators, including TNF-α, and iNOS expression as well as its inhibitory effect on oedema and PMN leucocyte infiltration.

Properties of novel surfactin-derived biosurfactants obtained through solid-phase synthesis.

Eight molecules, four peptides (SPs) and four lipopeptides (LPs) derived by rational design from surfactin, a well-known secreted biosurfactant from Bacillus subtilis, were produced employing Fmoc-based solid-phase synthesis. These new peptides were tested to evaluate their potential biosurfactant and biological activities, aiming at possible applications in industrial, biological, pharmaceutical, and medical use. Five molecules (SP1, SP2, SP4, LP5, and LP8) presented potential for medical uses, mainly due to their drug delivery properties as suggested by their synergistic activity with the antibiotic vancomycin against Staphylococcus aureus. All synthetic peptides showed low toxicity against Vero cell cultures, in assays of hemolysis, and in different cytotoxicity assays. In addition, we found that three peptides (SP1, LP6, and LP7) had potential technological and industrial use because of their emulsifying capacity, low toxicity, and ability to physically stabilize solutions. These novel molecules retained some properties of the parental molecule (surfactin, which was originally obtained through nonribosomal synthesis in Bacillus subtilis) but have the advantage of being linear peptides, which can be produced at large scales through the use of conventional heterologous protein expression protocols.

Ouabain Modulates the Lipid Composition of Hippocampal Plasma Membranes from Rats with LPS-induced Neuroinflammation.

The effects of ouabain (OUA) and lipopolysaccharide (LPS) in vivo on hippocampal membranes (RHM) of Wistar male rats aged 3 months were analyzed. After intraperitoneal (i.p.) injection of OUA only, LPS only, OUA plus LPS, or saline, the content of proteins, phospholipids, cholesterol and gangliosides from RHM was analyzed. The total protein and cholesterol contents of RHM were not significantly affected by OUA or LPS for the experimentally paired groups. In contrast, total phospholipids and gangliosides were strongly modulated by either OUA or LPS treatments. LPS reduced the total phospholipids (roughly 23 %) and increased the total gangliosides (approximately 40 %). OUA alone increased the total phospholipids (around 23 %) and also the total gangliosides (nearly 34 %). OUA pretreatment compensated the LPS-induced changes, preserving the total phospholipids and gangliosides around the same levels of the control. Thus, an acute treatment with OUA not only modulated the composition of hippocampal membranes from 3-month-old rats, but also was apparently able to counteract membrane alterations resulting from LPS-induced neuroinflammation. This study demonstrates for the first time that the OUA capacity modulates the lipid composition of hippocampal plasma membranes from rats with LPS-induced neuroinflammation.

Adverse reactions to docetaxel: an active survey

The rates of breast cancer mortality remain high in Brazil. Docetaxel is a semi-synthetic taxane used to treat various tumors, particularly tumors of the breast, lung and prostate. In this study ADR that occurred in 45 docetaxel users with breast cancer were surveyed. They were identified by type, causality (Naranjo algorithm and World Health Organization categories) and, if considered probable or defined, rated for severity according to SOBRAFO proposal (2007). A total of 325 ADR were observed: 165 in the first, 137 in the second and 23 in the third cycle. Fifty seven ADR were immediate and the others, late. Fatigue and exhaustion for more than five days, classified as Grade 3 by SOBRAFO (2007), were reported as the primary late RAM. There was no significant difference in the occurrence of immediate and late ADR between cycles (p=1 and p=0.3577, respectively). The presence of a pharmacist gave the patients a better understanding of the occurrence of RAM, especially those that occur outside the hospital, between chemotherapy cycles and are often not reported to the healthcare team, creating institutional demands and reaching the goal to track, observe and correlate the RAM for each user.

As taxas de mortalidade por câncer de mama no Brasil permanecem altas. O docetaxel é um taxano semi-sintético usado para tratar vários tumores, particularmente tumores da mama, pulmão e próstata. Neste estudo, as Reações Adversas (RAM) ocorridas em 45 pacientes com câncer de mama foram monitoradas. Elas foram classificadas pelo tipo e causalidade (Algoritmo de Naranjo e categorias propostas pela Organização Mundial da Saúde) e, se consideradas prováveis ou definidas, foram classificadas também pela severidade, de acordo com a proposta da SOBRAFO (2007). Um total de 325 RAM foram observadas: 165 no primeiro, 137 no segundo e 23 no terceiro ciclo. Cinquenta e sete RAM foram imediatas e as demais tardias. Fadiga e exaustão por mais de 5 dias, classificadas como grau 3 pela SOBRAFO (2007), foram as principais RAM encontradas. Não houve diferença significativa na ocorrência de RAM imediatas ou tardias entre os ciclos (p=1 e p=0,3577, respectivamente). A presença de um farmacêutico proporcionou aos pacientes um melhor entendimento sobre a ocorrência de RAM, especialmente sobre aquelas que ocorrem fora do ambiente hospitalar, entre os ciclos da terapia, não sendo usualmente relatadas aos profissionais de saúde. Isto gerou uma demanda na instituição e permitiu alcançar a meta de acompanhar, observar e correlacionar as RAM de cada paciente.

Efficacy of methotrexate-loaded poly(ε-caprolactone) implants in Ehrlich solid tumor-bearing mice.

CONTEXT: Methotrexate (MTX) is used in the treatment of malignancies; however, its clinical application is limited by its toxic dose-related side effects. An alternative to overcome the toxicity of the MTX in healthy tissues is the design of an implantable device capable of controlling the delivery of this drug for an extended period within the tumor site. OBJECTIVE: To develop methotrexate-loaded poly(ε-caprolactone) implants (MTX PCL implants) and to demonstrate their efficacy as local drug delivery systems capable of inhibiting Ehrlich solid tumor bearing mice. MATERIALS AND METHODS: MTX PCL implants were produced by the melt-molding technique and were characterized by FTIR, WAXS, DSC and SEM. The in vitro and in vivo release of MTX from the PCL implants was also evaluated. The efficacy of implants in inhibiting tumor cells in culture and the solid tumor in a murine model was revealed. RESULTS AND DISCUSSION: The chemical and morphological integrity of the drug was preserved into the polymeric matrix. The in vitro and in vivo release processes of the MTX from the PCL implants were modulated by diffusion. MTX diffused from the implants revealed an antiproliferative effect on tumor cells. Finally, MTX controlled and sustained released from the polymeric implants efficiently reduced 42.7% of the solid tumor in mice paw. CONCLUSION: These implantable devices represented a contribution to improve the efficacy and safety of chemotherapy treatments, promoting long-term local drug accumulation in the targeted site.

Carcinoma neuroendócrino de pequenas células de laringe: relato de caso erevisão da literatura / Small cell neuroendocrine carcinoma of the larynx: case report and literature revie

O presente relato de caso refere-se ao carcinomaneuroendócrino de pequenas células de laringe acometendouma mulher de 52 anos. Este carcinoma é umaneoplasia altamente maligna com metástases frequentese taxa de sobrevida baixa. Depois dos carcinomasespinocelulares, os tumores de laringe mais frequentessão os neuroendócrinos, que podem ser derivados decélulas neurais ou epiteliais. Os tumores neuroendócrinosderivados de epitélio podem ser classificados emquatro grupos patológicos bem definidos: tumor carcinoide,tumor carcinoide atípico, carcinoma neuroendócrinode pequenas células e carcinoma neuroendócrinode células grandes. Os carcinomas neuroendócrinos têmmorfologia distinta, entretanto apresentam perfil imunohistoquímicomarcado por algumas combinações depositividade para citoqueratina, cromogranina, sinaptofisina,CD56, CD57, enolase, serotonina, somatostatinae bombesina. Esses tumores da laringe apresentam umgrande espectro de evolução clínica, dependente dosubtipo histológico, que influencia significativamente oplanejamento de todo o tratamento.

This case report refers to small cell neuroendocrinecarcinoma of the larynx affecting a 52-year-old female.This is a highly malignant neoplasm with frequentmetastases and a lower survival rate. After squamouscarcinomas, the most frequent tumors of the larynx arethe neuroendocrine, these tumors can be derived fromneural or epithelial cells. Neuroendocrine tumors derivedfrom epithelium can be classified into four pathologicalcategories defined: carcinoid tumor, atypical carcinoidtumor, small cell neuroendocrine carcinoma andlarge cell neuroendocrine carcinoma. It is known thatdespite of having distinct morphology, neuroendocrinecarcinomas have immunohistochemical profile markedby some combination of positive for cytokeratin, chromogranin,synaptophysin, CD56, CD57, enolase, serotonin,somatostatin and bombesin. These laryngeal tumorsshow a broad spectrum of clinical, dependent onthe histological subtype, which influences the planningof the whole treatment.

Prevenção e controle da contaminação bacteriana de hemocomponentes / Prevención y control de la contaminación bacteriana de los productos sanguíneos / Prevention and control of bacterial contamination of blood products

Apesar do advento da genética molecular, terapia celular e automação de procedimentos, a possibilidadede transmissãode infecções por contaminação bacteriana dos componentes do sangue cresce em importância, sendo observada comoevento adverso à transfusão de sangue conhecido como reação transfusional por contaminação bacteriana.Foi verificadodurante as análises realizadas pelo controle de qualidade do Serviço de Hemoterapia que existe uma incidência variávelde contaminação bacteriana nas bolsas dos hemocomponentes do sangue. Estes dados demonstraram que parte dospacientes submetidos a transfusões de sangue poderiam estar expostos aos microrganismos presentes nasbolsas de sangueavaliadas como positivas pelo procedimento de cultura e, dessa forma, adquirir algum tipo de infecçãodevido a estacontaminação. Dentre todas as medidas de prevençãoe controle da contaminação bacteriana...

Despite the advent of molecular genetics, cell therapy and automation of procedures, the possibility of transmission ofinfection by bacterial contamination of blood components improves in importance, observing as an adverse event of bloodtransfusion the transfusion reaction known as bacterial contamination. During the analysis performed by the qualitycontrol of Hemoterapy Service it was found that there is a variable incidence of bacterial contamination of bloodcomponents in blood bags. These data showed that the proportion of patients undergoing blood transfusions could beexposed to microorganisms present in blood bags assessed as positive by the culture procedure and thuscould be acquiredsome kind of infection due to this contamination. Among all the measures of prevention and control ofbacterialcontamination of blood products, should be highlighted aseptic procedures appropriate to the puncturesite of the donor'sarm, as well as the sterilization of hands...

Apesar del advenimiento de la genética molecular,la terapia celular y la automatización de los procedimientos, laposibilidad de transmisión de la infección por contaminación bacteriana de los componentes de la sangre crece enimportancia, al ser visto como un evento adverso dela reacción a la transfusión conocido como reacción transfusional porcontaminación bacteriana. Se constató durante las pruebas realizadas para el control de calidad del Departamento deHematología que hay una incidencia variable de la contaminación bacteriana de los productos de la sangre en las bolsas desangre. Estos datos mostraron que la mayoría de lospacientes que se someten a transfusiones de sangrepodrían estarexpuestos a los microorganismos presentes en las bolsas de sangre evaluadas como positivas por el procedimiento decultura y, así, adquirir algún tipo de infección debido a esta contaminación. Entre todas las medidaspara prevenir ycontrolar la contaminación bacteriana de los productos sanguíneos, deben ser destacados los procedimientos de asepsiaadecuados para el sitio de punción del brazo del donante, así como los de limpieza de las manos, que habitualmentedeben ser incorporados en todos los bancos de sangre; además del uso de guantes desechables durante laejecución detodas las actividades. Estas medidas no solo objetivan proteger todos los profesionales implicados, sino también evitar elriesgo de infecciones nosocomiales provocadas por componentes...