A Liposome Encapsulated Ruthenium Polypyridine Complex as a Theranostic Platform for Triple-Negative Breast Cancer.

Ruthenium coordination complexes have the potential to serve as novel theranostic agents for cancer. However, a major limitation in their clinical implementation is effective tumor accumulation. In this study, we have developed a liposome-based theranostic nanodelivery system for [Ru(phen)2dppz](ClO4)2 (Lipo-Ru). This ruthenium polypyridine complex emits a strong fluorescent signal when incorporated in the hydrophobic lipid bilayer of the delivery vehicle or in the DNA helix, enabling visualization of the therapeutic agent in tumor tissues. Incubation of MDA-MB-231 breast cancer cells with Lipo-Ru induced double-strand DNA breaks and triggers apoptosis. In a mouse model of triple-negative breast cancer, treatment with Lipo-Ru dramatically reduced tumor growth. Biodistribution studies of Lipo-Ru revealed that more than 20% of the injected dose accumulated in the tumor. These results suggest that Lipo-Ru could serve as a promising theranostic platform for cancer.

Positivity rates of drugs in patients treated for opioid dependence with buprenorphine: A comparison of oral fluid and urine using paired collections and LC-MS/MS.

BACKGROUND: Drug testing is recommended as part of comprehensive monitoring for medication-assisted treatment. Alternative matrices including oral fluid offer a number of advantages when compared with conventional urine testing but are not as well characterized. This study aims to compare positivity rates of drugs and drug classes in oral fluid and urine as a measure of the clinical utility of oral fluid in the evaluation and treatment of patients with opioid use disorders. METHODS: A retrospective review of paired oral fluid and urine test results from Millennium Health's laboratory database was performed for 2746 patients with reported prescriptions for buprenorphine products used in the treatment of opioid dependence. Specimens were tested using quantitative LC-MS/MS for 34 medications, metabolites and illicit drugs. RESULTS: A number of medications and illicit drugs were detected at comparable or higher rates in oral fluid vs. urine such as cocaine (15.7% vs. 7.9%), opiates (13.4% vs. 10.0%), oxycodone (8.6% vs. 3.7%), hydrocodone (3.0% vs. 1.2%) and others. Lower detection rates were observed in oral fluid vs. urine for benzodiazepines (6.6% vs. 8.7%), cannabinoids (15.5% vs. 19.5%), oxymorphone (1.8% vs. 3.1%) and hydromorphone (0.8% vs. 4.5%). CONCLUSIONS: Clinicians may find oral fluid advantageous for detection of specific drugs and medications in certain clinical situations. Understanding the relative differences between urine and oral fluid can help clinicians carefully select tests best suited for detection in their respective matrix. To our knowledge, this is the largest inter-matrix patient comparison study using paired collections and direct to definitive testing.

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination.

mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(ß-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell. This core-shell structured mRNA vaccine enters dendritic cells through macropinocytosis. It displayed intrinsic adjuvant activity by potently stimulating interferon-ß and interleukin-12 expression in dendritic cells through Toll-like receptor 7/8 signaling. Dendritic cells treated with the mRNA vaccine displayed enhanced antigen presentation capability. Mice bearing lung metastatic B16-OVA tumors expressing the ovalbumin antigen were treated with the lipopolyplex mRNA, and over 90% reduction of tumor nodules was observed. Collectively, this core-shell structure offers a promising platform for mRNA vaccine development.

Cohortes de premedicación en endoscopia alta con simeticona, N-acetilcisteína, Hedera helix y validación de la escala visual / Cohorts of premedication for endoscopy of the upper gastrointestinal tract with simethicone, N-acetylcysteine, Hedera helix and visual scale validation

Resumen Los parámetros de calidad para endoscopia digestiva alta han introducido indicadores intraprocedimiento, dentro de los cuales la adecuada visibilidad de la mucosa, libre de saliva, moco o burbujas, puede aumentar la posibilidad de detección de lesiones en fase temprana. Sin embargo, el uso de mucolíticos y antiburbujas ha mostrado gran variabilidad de eficiencia según las soluciones, concentraciones, tiempos de exposición y escala de visibilidad aplicados. Objetivos: determinar la efectividad de diferentes soluciones de premedicación para la limpieza de la mucosa digestiva; validar, mediante una prueba de concordancia interobservador, una nueva escala de adecuada visualización de la mucosa (TVMS) para el esófago, estómago y duodeno; y reportar eventos adversos o complicaciones relacionadas con las soluciones utilizadas y los procedimientos realizados. Material y métodos: estudio de cohortes prospectivas comparativas. Se incluyeron 412 pacientes adultos, ASA I y ASA II, para endoscopia diagnóstica bajo sedación consciente, distribuidos en 6 cohortes similares, divididas en dos grupos: no premedicación, 2 cohortes C1 (ayuno de 6 a 8 horas)y C2 (agua 100 mL); premedicación, 4 cohortes C3 a C6 (C3: agua 100 m L + simeticona 1000 mg; C4: agua 100 mL + simeticona 200 mg + N-acetilcisteína 600 mg; C5: agua 100 mL + simeticona 200 mg + N-acetilcisteína 1000 mg; C6: agua 100 mL + simeticona 200 mg + Hedera helix 70 mg). Se ingirió la solución 15 a 30 minutos antes del paso por cricofaríngeo. Se realizó la prueba de Kappa para medir la concordancia interobservador de la escala TVMS. Resultados: De 412 pacientes, 58% fueron de sexo femenino; 23% (136) fue de cohortes C1 y C2 y 67% (276) fue de cohortes C3 a C6. El tiempo medio de exposición a cada solución fue de 24,4 minutos. El volumen de lavado para lograr una adecuada visualización fue significativamente diferente entre ambos grupos: en los pacientes con premedicación se utilizaron 75,6 mL, mientras que en los pacientes sin premedicación se utilizaron 124 mL (p = 0,000), con una calidad de TVMS excelente de 88,7% frente al 41,4%, respectivamente. La cohorte C4 (agua 100 mL + simeticona 200 mg + N-acetilcisteína 600 mg) mostró ser la más efectiva con una diferencia significativa (p = 0,001) frente a C1 (ayuno) y C2 (placebo con agua 100 mL), y también tuvo una eficiencia superior frente a C3, C5 y C6 en su orden. No se presentaron eventos adversos o complicaciones en relación con la endoscopia, la sedación y los productos usados en la premedicación. Conclusiones: la solución más efectiva como premedicación para lograr una excelente visibilidad de la mucosa digestiva correspondió a la cohorte C4 (SIM 200 + NAC 600 + H2O 100 mL). La escala TVMS propuesta es una herramienta muy completa y fácil de aplicar por más de un observador. La premedicación ingerida, con antiburbuja, mucolítico y agua hasta 100 mL, entre 15 y 30 minutos previos a endoscopia, es segura en las condiciones descritas en este estudio.

Abstract Quality parameters for upper gastrointestinal endoscopy have introduced intraprocedural indicators, including adequate mucosal visualization free of saliva, mucus, or bubbles, which may increase the possibility of early-stage injury detection. The use of mucolytics and anti-foaming agents has shown great efficiency variability depending on the type of solution, concentrations, exposure times and visibility scale applied. Objectives: To determine the effectiveness of different premedication solutions for cleaning the digestive mucosa; to validate, by means of an interobserver concordance test, a new scale for the adequate visualization of the mucosa (TVMS) for the esophagus, stomach, and duodenum; and to report adverse events or complications associated with the solutions used and the procedures performed. Material and methods: Prospective, comparative cohort study. 412 adult patients, ASA I and ASA II, were included for diagnostic endoscopy under conscious sedation. They were distributed in 6 similar cohorts and divided into two groups: non-premedication, 2 in C1 (fasting 6 to 8 hours) and C2 (water 100 mL) cohorts; premedication, 4 C3 to C6 cohorts (C3: water 100 mL + simethicone 1000 mg; C4: water 100 ml + simethicone 200 mg + N-acetylcysteine 600 mg; C5: water 100 ml + simethicone 200 mg + N-acetylcysteine 1000 mg; C6: water 100 ml + simethicone 200 mg + Hedera helix 70 mg). The solution was swallowed 15 to 30 minutes passing through the cricopharyngeus muscle. The Kappa test was performed to measure interobserver concordance of the TVMS scale. Results: Of 412 patients, 58% were female; 23% (136) were included in the C1 and C2 cohorts; and 67% (276) were in the C3 to C6 cohorts. The average exposure time to each solution was 24.4 minutes. The wash volume for proper visualization was significantly different between the two groups. In premedicated patients, 75.6 mL of solution were used, while in patients without premedication, 124 mL were used (p = 0.000), with an excellent quality of TVMS of 88.7% versus 41.4%, respectively. The C4 cohort (water 100 mL + simethicone 200 mg + N-acetylcysteine 600 mg) was the most effective with a significant difference (p= 0.001) compared with the C1 (fasting) and C2 (placebo with water 100 mL) cohorts. It also had better efficiency compared to the C3, C5 and C6 cohorts in that order. There were no adverse events or complications associated with endoscopy, sedation, or premedication products. Conclusions: The most effective solution as a premedication to achieve excellent visibility of the digestive mucosa was that used in the C4 cohort (SIM 200 + NAC 600 + H2OR 100 mL). The proposed TVMS scale is a very complete and easy tool to apply by more than one observer. Premedication ingested, with anti-foam, mucolytic and water up to 100 mL, between 15 and 30 minutes before endoscopy, is safe under the conditions described in this study.

[Oral fluid and urine as alternative samples in confirmatory testing of HIV-1 infection]. / Fluido oral y orina como muestras alternativas en el diagnóstico confirmatorio de la infección por VIH-1.

The objective of this report was to evaluate oral fluid and urine as optional samples for HIV-1 confirmatory test using DAVIH-BLOT system (Laboratorios DAVIH, La Habana, Cuba), for which they were compared with their corresponding serum samples in a group of 125 individuals. In band pattern analysis, predominant antibodies in positives oral fluid and urine samples against p34, p68, gp41, gp120, were no different from their corresponding sera according to the proportion comparison test (p < 0,001). Relative sensitivity and specificity of this system were 100% in oral fluid and 98, 75% and 100% in urine samples respectively. These results support optional use of oral fluid and urine that, with slight modifications in the diagnostic system, can be applied for HIV-1 antibody confirmation testing.

Fluido oral y orina como muestras alternativas en el diagnóstico confirmatorio de la infección por VIH-1 / Oral fluid and urine as alternative samples in confirmatory testing of HIV-1 infection

Se evaluó el fluido oral y la orina como muestras opcionales en el diagnóstico confirmatorio del VIH-1 con el sistema DAVIH-BLOT (Laboratorios DAVIH, La Habana, Cuba), para lo cual se comparó con las correspondientes muestras de sueros en un grupo de 125 individuos. En el análisis de los patrones de bandas reveladas, los anticuerpos predominantes en las muestras positivas de fluido oral y orina contra la p34, p68, gp41 y gp120, no tuvieron diferencias con sus correspondientes sueros según la prueba de comparación de proporciones (p< 0,001). La sensibilidad y especificidad relativas del sistema resultaron de 100 por ciento en el análisis del fluido oral; 98,75 y 100 por ciento, respectivamente, en las muestras de orina. Estos resultados apoyan el empleo opcional del fluido oral y la orina que, con ligeras modificaciones introducidas en el sistema diagnóstico, pueden aplicarse para la confirmación de anticuerpos contra el VIH-1.

The objective of this report was to evaluate oral fluid and urine as optional samples for HIV-1 confirmatory test using DAVIH-BLOT system (Laboratorios DAVIH, La Habana, Cuba), for which they were compared with their corresponding serum samples in a group of 125 individuals. In band pattern analysis, predominant antibodies in positives oral fluid and urine samples against p34, p68, gp41, gp120, were no different from their corresponding sera according to the proportion comparison test (p<0,001). Relative sensitivity and specificity of this system were 100 pernent in oral fluid and 98, 75 pernent and 100 pernent in urine samples respectively. These results support optional use of oral fluid and urine that, with slight modifications in the diagnostic system, can be applied for HIV-1 antibody confirmation testing.

Ulceras esofágicas producidas por medicamentos: informe de un paciente / Esophageal ulcers produced by drugs: report of a patient

Se describe un caso de un paciente quien despúes de la ingesta de varios comprimidos de naproxen, un antiinflamatorio no esteroide, presentó disfagia y dolor retoesternal muy severo, con irradiación a la espalda. La esofagoscopía mostró una zona de ulceraciones superficiales y edema a unos 28 cm de la arcada dentaria. La suspensión de la medicación y la administración de gel de hidróxido de aluminio y metoclopramida permitieron la rápida solución del problema. En la literatura se encuentran varias comunicaciones incluyendo hasta el momento unos 26 medicamentos potencialmente peligrosos para la mucosa esofágica. Se discuten los posibles mecanismos de producción de este tipo de lesiones