RESUMO

RESUMEN La embolia cerebral paradójica siempre requiere la presencia de foramen oval; en nuestro caso, este evento sucedió por un fenómeno temporal, el cual fue la sobrecarga aguda de las cavidades derechas y la apertura del foramen oval debido al aumento de presiones como consecuencia de un tromboembolismo pulmonar masivo. Luego de una artroscopía, nuestra paciente presentó pérdida del campo visual y disnea, esta última progresiva, hasta llegar a la ventilación mecánica y shock obstructivo grave. Se realizó una angiotomografía, la cual evidenció un trombo obstructivo en la arterial pulmonar derecha; la paciente fue trombolizada con éxito y fue dada de alta de la unidad de cuidados intensivos después de 45 días. Finalmente se le diagnosticó una deficiencia de proteína C y se inició anticoagulación de manera permanente. La presencia de déficit motor y disnea en una paciente post-cirugía de rodilla, debe hacer sospechar de una tromboembolia pulmonar, la trombólisis sigue siendo el tratamiento de elección, su indicación debe ser precoz.

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ABSTRACT Paradoxical cerebral embolism always requires the presence of a patent foramen ovale (PFO); in our case, this event occurred due to a transient phenomenon, which was the acute overload of the right heart chambers and the opening of the PFO due to increased pressures as a consequence of massive pulmonary thromboembolism. After undergoing arthroscopy, this patient presented with visual field loss and progressive dyspnea, ultimately leading to mechanical ventilation and severe obstructive shock. An angiotomography was performed, revealing an obstructive thrombus in the right pulmonary artery. The patient successfully underwent thrombolysis, and she was discharged from the intensive care unit after 45 days. Ultimately, protein C deficiency was diagnosed, and permanent anticoagulation was initiated. The presence of motor deficit and dyspnea in a post-knee surgery patient should raise suspicion of pulmonary thromboembolism. Thrombolysis remains the treatment of choice, and it should be timely prescribed and performed.

RESUMO

RESUMEN Objetivo. Describir las principales características demográficas, clínicas, laboratoriales y terapéuticas e identificar si están asociados con la mortalidad en pacientes traqueostomizados. Material y métodos. Estudio de cohorte retrospectiva en pacientes adultos con diagnóstico de COVID-19, ingresados a UCI (Unidad de Cuidados Intensivos) y que requirieron traqueostomía. Se extrajeron datos demográficos, clínicos, laboratoriales y de tratamiento de las historias clínicas de pacientes que ingresaron al Hospital III Daniel Alcides Carrión de Tacna. Para el análisis de supervivencia se empleó el modelo de riesgos proporcionales de Cox y se calcularon los cocientes de riesgo instantáneos (HR) con sus intervalos de confianza al 95% (IC95%). Resultados. Se evaluaron 73 pacientes, el 72,6% eran hombres, las comorbilidades más comunes fueron obesidad (68,5%), diabetes mellitus tipo 2 (35,6%) e hipertensión arterial (34,2%). El 37% de los participantes fallecieron durante la estancia en UCI. La mediana de tiempo desde la intubación hasta la traqueostomía y la duración de esta fue 17 (RIC: 15−21) y 21 (RIC: 3−39) días, respectivamente. El análisis multivariado mostró que los factores asociados a mortalidad, fueron presentar un valor de procalcitonina > 0,50 ng/dL en el momento de la traqueostomía (HRa: 2,40 IC95%: 1,03−5,59) y el nivel de PaO2/FiO2 menor o igual a 150 mmHg, (HRa: 4,44 IC95%: 1,56−12,60). Conclusiones. Los factores asociados a mortalidad al momento de realizar la traqueostomía fueron presentar un valor de procalcitonina > 0,50 ng/dL y un cociente PaO2/FiO2 menor o igual a 150 mmHg.

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ABSTRACT Objective: We aimed to describe the main demographic, clinical, laboratory and therapeutic characteristics and to identify whether they are associated with mortality in tracheostomized patients. Material and methods. Retrospective cohort study in adult patients diagnosed with COVID-19, admitted to ICU (Intensive Care Unit) and requiring tracheostomy. Demographic, clinical, laboratory and treatment data were obtained from the medical records of patients admitted to Hospital III Daniel Alcides Carrión in Tacna. The Cox proportional hazards model was used for survival analysis and hazard ratios (HR) with their 95% confidence intervals (95%CI) were calculated. Results. We evaluated 73 patients, 72.6% were men, the most common comorbidities were obesity (68.5%), type 2 diabetes mellitus (35.6%), and arterial hypertension (34.2%). Thirty-seven percent of the participants died during their stay at the ICU. The median time from intubation to tracheostomy and the duration of tracheostomy was 17 (RIC: 15-21) and 21 (RIC: 3-39) days, respectively. Multivariate analysis showed that the factors associated with mortality were procalcitonin > 0.50 ng/dL at the time of tracheostomy (HRa: 2.40 95%CI: 1.03-5.59) and a PaO2/FiO2 ratio less than or equal to 150 mmHg (HRa: 4.44 95%CI: 1.56-12.60). Conclusions. The factors associated with mortality at the time of tracheostomy were procalcitonin > 0.50 ng/dL and a PaO2/FiO2 ratio less than or equal to 150 mmHg.

Assuntos

Humanos , Masculino , Feminino , Traqueotomia

RESUMO

Alternative therapies such as photodynamic therapy (PDT) that combine light, oxygen and photosensitizers (PSs) have been proposed for glioblastoma (GBM) management to overcome conventional treatment issues. An important disadvantage of PDT using a high light irradiance (fluence rate) (cPDT) is the abrupt oxygen consumption that leads to resistance to the treatment. PDT metronomic regimens (mPDT) involving administering light at a low irradiation intensity over a relatively long period of time could be an alternative to circumvent the limitations of conventional PDT protocols. The main objective of the present work was to compare the effectiveness of PDT with an advanced PS based on conjugated polymer nanoparticles (CPN) developed by our group in two irradiation modalities: cPDT and mPDT. The in vitro evaluation was carried out based on cell viability, the impact on the macrophage population of the tumor microenvironment in co-culture conditions and the modulation of HIF-1α as an indirect indicator of oxygen consumption. mPDT regimens with CPNs resulted in more effective cell death, a lower activation of molecular pathways of therapeutic resistance and macrophage polarization towards an antitumoral phenotype. Additionally, mPDT was tested in a GBM heterotopic mouse model, confirming its good performance with promising tumor growth inhibition and apoptotic cell death induction.

Assuntos

Glioblastoma , Nanopartículas , Fotoquimioterapia , Camundongos , Animais , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Fotoquimioterapia/métodos , Polímeros , Microambiente Tumoral , Linhagem Celular Tumoral

RESUMO

In recent years significant efforts have been made to develop new materials for wound dressing with improved healing properties. However, the synthesis methods usually employed to this end are often complex or require several steps. We describe here the synthesis and characterization of antimicrobial reusable dermatological wound dressings based on N-isopropylacrylamide co-polymerized with [2-(Methacryloyloxy) ethyl] trimethylammonium chloride hydrogels (NIPAM-co-METAC). The dressings were obtained with a very efficient single-step synthesis procedure based on visible light (455 nm) by photopolymerization. To this end, F8BT nanoparticles of the conjugated polymer (poly(9,9-dioctylfluorene-alt-benzothiadiazole) - F8BT) were used as macro-photoinitiators, and a modified silsesquioxane was employed as crosslinker. Dressings obtained by this simple and gentle method show antimicrobial and wound healing properties, without the incorporation of antibiotics or any other additives. The physical and mechanical properties of these hydrogel-based dressings were evaluated, as well as their microbiological properties, through in vitro experiments. Results show that dressings with a molar ratio of METAC of 0.5 or higher exhibit high swelling capacity, appropriate water vapor transmission rate values, stability and thermal response, high ductility and adhesiveness. In addition, biological tests showed that the dressings have significant antimicrobial capacity. The best inactivation performance was found for hydrogels synthesized with the highest METAC content. The dressings were tested several times with fresh bacterial cultures, showing a bacterial kill efficiency of 99.99 % even after three repetitions in a row, employing the same dressing, demonstrating the intrinsic bactericidal property of the materials and their reusability. In addition, the gels show low hemolytic effect, high dermal biocompatibility and noticeable wound healing effects. Overall results demonstrate that some specific hydrogel formulations have potential application as dermatological dressings for wound healing and disinfection.

Assuntos

Antibacterianos , Anti-Infecciosos , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Cicatrização , Bandagens , Hidrogéis/farmacologia

RESUMO

OBJECTIVE: We aimed to describe the main demographic, clinical, laboratory and therapeutic characteristics and to identify whether they are associated with mortality in tracheostomized patients. MATERIAL AND METHODS.: Retrospective cohort study in adult patients diagnosed with COVID-19, admitted to ICU (Intensive Care Unit) and requiring tracheostomy. Demographic, clinical, laboratory and treatment data were obtained from the medical records of patients admitted to Hospital III Daniel Alcides Carrión in Tacna. The Cox proportional hazards model was used for survival analysis and hazard ratios (HR) with their 95% confidence intervals (95%CI) were calculated. RESULTS.: We evaluated 73 patients, 72.6% were men, the most common comorbidities were obesity (68.5%), type 2 diabetes mellitus (35.6%), and arterial hypertension (34.2%). Thirty-seven percent of the participants died during their stay at the ICU. The median time from intubation to tracheostomy and the duration of tracheostomy was 17 (RIC: 15-21) and 21 (RIC: 3-39) days, respectively. Multivariate analysis showed that the factors associated with mortality were procalcitonin > 0.50 ng/dL at the time of tracheostomy (HRa: 2.40 95%CI: 1.03-5.59) and a PaO2/FiO2 ratio less than or equal to 150 mmHg (HRa: 4.44 95%CI: 1.56-12.60). CONCLUSIONS.: The factors associated with mortality at the time of tracheostomy were procalcitonin > 0.50 ng/dL and a PaO2/FiO2 ratio less than or equal to 150 mmHg.

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OBJETIVO.: Describir las principales características demográficas, clínicas, laboratoriales y terapéuticas e identificar si están asociados con la mortalidad en pacientes traqueostomizados. MATERIAL Y MÉTODOS.: Estudio de cohorte retrospectiva en pacientes adultos con diagnóstico de COVID-19, ingresados a UCI (Unidad de Cuidados Intensivos) y que requirieron traqueostomía. Se extrajeron datos demográficos, clínicos, laboratoriales y de tratamiento de las historias clínicas de pacientes que ingresaron al Hospital III Daniel Alcides Carrión de Tacna. Para el análisis de supervivencia se empleó el modelo de riesgos proporcionales de Cox y se calcularon los cocientes de riesgo instantáneos (HR) con sus intervalos de confianza al 95% (IC95%). RESULTADOS.: Se evaluaron 73 pacientes, el 72,6% eran hombres, las comorbilidades más comunes fueron obesidad (68,5%), diabetes mellitus tipo 2 (35,6%) e hipertensión arterial (34,2%). El 37% de los participantes fallecieron durante la estancia en UCI. La mediana de tiempo desde la intubación hasta la traqueostomía y la duración de esta fue 17 (RIC: 15−21) y 21 (RIC: 3−39) días, respectivamente. El análisis multivariado mostró que los factores asociados a mortalidad, fueron presentar un valor de procalcitonina > 0,50 ng/dL en el momento de la traqueostomía (HRa: 2,40 IC95%: 1,03−5,59) y el nivel de PaO2/FiO2 menor o igual a 150 mmHg, (HRa: 4,44 IC95%: 1,56−12,60). CONCLUSIONES.: Los factores asociados a mortalidad al momento de realizar la traqueostomía fueron presentar un valor de procalcitonina > 0,50 ng/dL y un cociente PaO2/FiO2 menor o igual a 150 mmHg.

Assuntos

COVID-19 , Diabetes Mellitus Tipo 2 , Síndrome do Desconforto Respiratório , Masculino , Adulto , Humanos , Feminino , Estudos Retrospectivos , Peru , Pró-Calcitonina , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Hospitais

RESUMO

Photodynamic therapy (PDT) may be an excellent alternative in the treatment of breast cancer, mainly for the most aggressive type with limited targeted therapies such as triple-negative breast cancer (TNBC). We recently generated conjugated polymer nanoparticles (CPNs) as efficient photosensitizers for the photo-eradication of different cancer cells. With the aim of improving the selectivity of PDT with CPNs, the nanoparticle surface conjugation with unique 2'-Fluoropyrimidines-RNA-aptamers that act as effective recognition elements for functional surface signatures of TNBC cells was proposed and designed. A coupling reaction with carbodiimide was used to covalently bind NH2-modified aptamers with CPNs synthetized with two polystyrene-based polymer donors of COOH groups for the amide reaction. The selectivity of recognition for TNBC membrane receptors and PDT efficacy were assayed in TNBC cells and compared with non-TNBC cells by flow cytometry and cell viability assays. Furthermore, in vitro PDT efficacy was assayed in different TNBC cells with significant improvement results using CL4, sTN29 and sTN58 aptamers compared to unconjugated CPNs and SCR non-specific aptamer. In a chemoresistance TNBC cell model, sTN58 was the candidate for improving labelling and PDT efficacy with CPNs. We proposed sTN58, sTN29 and CL4 aptamers as valuable tools for selective TNBC targeting, cell internalization and therapeutic improvements for CPNs in PDT protocols.

RESUMO

OBJECTIVE: To describe the clinical, laboratory and treatment characteristics of COVID-19 patients and to determine the factors associated with mortality during hospital stay. Materials and Methods: Retrospective cohort study of adult COVID-19 inpatients. The clinical, laboratory and treatment data were obtained from the medical records of patients from the Hospital Nivel III Daniel Alcides Carrión in Tacna. For the survival analysis we used the Cox proportional hazards model, and we calculated crude and adjusted hazard ratios (HR) with 95% confidence intervals (95% CI). RESULTS: We evaluated 351 patients; 74.1% of them were men. The most common comorbidities were obesity (31.6%), hypertension (27.1%) and diabetes mellitus (24.5%). The median time of hospitalization was 8 days (IQR: 4-15). From the total of patients, 32.9% died during follow-up. The multivariate analysis showed an increased risk of dying associated with the following: age ≥65 years, HR = 3.55 (95% CI: 1.70-7.40); increase in lactate dehydrogenase >720 U/L, HR = 2.08 (95% CI: 1.34-3.22); and oxygen saturation less than 90%, mainly when it was less than 80%, HR = 4.07 (95% CI: 2.10-7.88). In addition, the use of colchicine during treatment showed a protective effect, HR = 0.46 (95% CI: 0.23-0.91). CONCLUSIONS: Risk factors for mortality due to COVID-19 included being older than 65 years, having oxygen saturation less than 90%, and elevated lactate dehydrogenase >720 U/L; colchicine treatment could improve the prognosis of patients.

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OBJETIVO: Describir las características demográficas, clínicas, laboratoriales y de tratamiento de pacientes hospitalizados por la COVID-19 y determinar los factores asociados a la mortalidad hospitalaria. MATERIALES Y MÉTODOS: Estudio de cohorte retrospectivo de pacientes adultos hospitalizados por la COVID-19. Se extrajeron datos demográficos, clínicos, laboratoriales y de tratamiento de las historias clínicas de pacientes que ingresaron al Hospital III Daniel Alcides Carrión de Tacna. Para el análisis de supervivencia se empleó el modelo de riesgos proporcionales de Cox y se calcularon los cocientes de riesgo instantáneos (HR) crudos y ajustados con sus respectivos intervalos de confianza al 95% (IC 95%). RESULTADOS: Se evaluó a 351 pacientes, el 74,1% eran hombres; las comorbilidades más comunes fueron obesidad (31,6%), hipertensión (27,1%) y diabetes mellitus (24,5%). La mediana de tiempo de hospitalización fue 8 días (RIC: 4-15). El 32,9% falleció durante el seguimiento. El análisis multivariado mostró un aumento del riesgo de morir asociado a la edad ≥65 años, HR = 3,55 (IC 95%: 1,70-7,40); al incremento de lactato deshidrogenasa >720 U/L, HR = 2,08 (IC 95%: 1,34-3,22); y a la saturación de oxígeno por debajo del 90%, principalmente cuando fue menor al 80%, HR = 4,07 (IC 95%: 2,10-7,88). Además, el uso de colchicina en el tratamiento tuvo un efecto protector, HR = 0,46 (IC 95%: 0,23-0,91). CONCLUSIONES: Los factores asociados a muerte por la COVID-19 incluyeron ser mayor de 65 años, tener saturación de oxígeno menor de 90% y elevación del lactato deshidrogenasa >720 U/L; el tratamiento con colchicina podría mejorar el pronóstico de los pacientes.

Assuntos

COVID-19 , Adulto , Idoso , Comorbidade , Mortalidade Hospitalar , Hospitalização , Hospitais Públicos , Humanos , Masculino , Peru/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2

RESUMO

RESUMEN Se realizó un estudio descriptivo en el que se evaluaron las características clínicas y laboratoriales en la evolución de pacientes con diagnóstico de síndrome de distrés respiratorio agudo (SDRA) secundario a infección por SARS-CoV-2 y que recibieron Tocilizumab. Veinticuatro pacientes recibieron Tocilizumab, la mayoría eran varones (95,8 %), la comorbilidad más frecuente fue obesidad (33,3 %), al momento de recibir Tocilizumab la mediana de PaO2/FiO2 fue 159,5 (RIC 114,5-255,3). Veintiún (87,5 %) pacientes presentaron mejoría clínica y 3 (12,5 %) fallecieron. Quince pacientes (62,5 %) desarrollaron hepatotoxicidad, la mayoría de grado 3 (33,3 %) y tres (12,5 %) pacientes presentaron injuria hepática grado 4. Once pacientes (45,8 %) presentaron sobreinfección bacteriana, siendo el germen más frecuente Acinetobacter baumannii. Luego de la administración de Tocilizumab más de la mitad de los pacientes presentó una reacción adversa, a pesar de ello la mortalidad fue baja y la mayoría tuvo una mejora clínica.

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ABSTRACT A descriptive study was carried out, in which clinical and laboratory characteristics were evaluated in patients with a diagnosis of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection and who received Tocilizumab. Twenty- four patients received Tocilizumab, the majority were male (95.8%), the most frequent comorbidity was obesity (33.3%). At the time of receiving Tocilizumab the median PAO2 / FiO2 was 159.5 (IQR 114.5-255, 3). Twenty-one (87.5%) patients presented clinical improvement and 3 (12.5%) died. Fifteen patients (62.5%) developed hepatotoxicity, the majority grade 3 (33.3%) and three (12.5%) patients presented grade 4 liver injury. Eleven patients (45.8%) presented bacterial superinfection, the more common organism being Acinetobacter baumannii. After the administration of Tocilizumab, more than half of the patients presented an adverse reaction; despite this, mortality was low, and the majority had a clinical improvement.

RESUMO

Glioblastoma is the most severe form of brain cancer. Despite multimodal therapy combining surgery, radiotherapy and chemotherapy, prognosis of patients is dismal. It has been observed that the surgical resection guided by photosensitizer fluorescence followed by photodynamic therapy (PDT) prolongs the average survival in patients with glioblastoma. The main problem with all oncological treatments, including PDT, is the presence of resistant cells. The objective of this study was to isolate and perform an initial characterization of human glioblastoma cells resistant to PDT employing methyl-5-aminolevulinic acid. We obtained resistant cells from the T98 G cell line. Resistant populations accumulated less photosensitizer, formed spheroids of higher number of cells, had higher tumorigenic capacity, and expressed higher mRNA levels of fibroblastic growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and ß-platelet-derived growth factor receptor (ßPDGFR) than parental cells. The studies of glioblastoma resistance to PDT would help to better understand the causes of tumor recurrence after PDT and to develop new therapeutic proposals in this field of oncology.

Assuntos

Glioblastoma , Fotoquimioterapia , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/uso terapêutico , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico

RESUMO

Objetivo: Describir las características demográficas, clínicas, laboratoriales y de tratamiento de pacientes hospitalizados por la COVID-19 y determinar los factores asociados a la mortalidad hospitalaria. Materiales y métodos: Estudio de cohorte retrospectivo de pacientes adultos hospitalizados por la COVID-19. Se extrajeron datos demográficos, clínicos, laboratoriales y de tratamiento de las historias clínicas de pacientes que ingresaron al Hospital III Daniel Alcides Carrión de Tacna. Para el análisis de supervivencia se empleó el modelo de riesgos proporcionales de Cox y se calcularon los cocientes de riesgo instantáneos (HR) crudos y ajustados con sus respectivos intervalos de confianza al 95% (IC 95%). Resultados: Se evaluó a 351 pacientes, el 74,1% eran hombres; las comorbilidades más comunes fueron obesidad (31,6%), hipertensión (27,1%) y diabetes mellitus (24,5%). La mediana de tiempo de hospitalización fue 8 días (RIC: 4-15). El 32,9% falleció durante el seguimiento. El análisis multivariado mostró un aumento del riesgo de morir asociado a la edad ≥65 años, HR = 3,55 (IC 95%: 1,70-7,40); al incremento de lactato deshidrogenasa >720 U/L, HR = 2,08 (IC 95%: 1,34-3,22); y a la saturación de oxígeno por debajo del 90%, principalmente cuando fue menor al 80%, HR = 4,07 (IC 95%: 2,10-7,88). Además, el uso de colchicina en el tratamiento tuvo un efecto protector, HR = 0,46 (IC 95%: 0,23-0,91). Conclusiones: Los factores asociados a muerte por la COVID-19 incluyeron ser mayor de 65 años, tener saturación de oxígeno menor de 90% y elevación del lactato deshidrogenasa >720 U/L; el tratamiento con colchicina podría mejorar el pronóstico de los pacientes.

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Objective: To describe the clinical, laboratory and treatment characteristics of COVID-19 patients and to determine the factors associated with mortality during hospital stay. Materials and Methods: Retrospective cohort study of adult COVID-19 inpatients. The clinical, laboratory and treatment data were obtained from the medical records of patients from the Hospital Nivel III Daniel Alcides Carrión in Tacna. For the survival analysis we used the Cox proportional hazards model, and we calculated crude and adjusted hazard ratios (HR) with 95% confidence intervals (95% CI). Results: We evaluated 351 patients; 74.1% of them were men. The most common comorbidities were obesity (31.6%), hypertension (27.1%) and diabetes mellitus (24.5%). The median time of hospitalization was 8 days (IQR: 4-15). From the total of patients, 32.9% died during follow-up. The multivariate analysis showed an increased risk of dying associated with the following: age ≥65 years, HR = 3.55 (95% CI: 1.70-7.40); increase in lactate dehydrogenase >720 U/L, HR = 2.08 (95% CI: 1.34-3.22); and oxygen saturation less than 90%, mainly when it was less than 80%, HR = 4.07 (95% CI: 2.10-7.88). In addition, the use of colchicine during treatment showed a protective effect, HR = 0.46 (95% CI: 0.23-0.91). Conclusions: Risk factors for mortality due to COVID-19 included being older than 65 years, having oxygen saturation less than 90%, and elevated lactate dehydrogenase >720 U/L; colchicine treatment could improve the prognosis of patients.

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Pneumonia Viral , Fatores de Risco , Sobrevivência

RESUMO

Due to their superb light absorption and photostability conjugated polymer nanoparticles are promising photosensitizers (PS) for their use in Photodynamic therapy (PDT). Recently, we developed metallated porphyrin-doped conjugated polymer nanoparticles (CPNs) for PDT that efficiently eliminate tumor cells through reactive oxygen species (ROS) mediated photoinduced damage of apoptotic nature. These nanoaggregates act as densely packed multi-chromophoric systems having exceptional light harvesting and (intra-particle) energy transfer capabilities which lead to efficient photosensitized formation of ROS. In general, three key components; light, PS, and oxygen; are considered in the prediction of the PDT outcome. However, recent studies led to the discovery of a profound genetic heterogeneity among glioblastoma (GBM) cells which include the adaptation to ROS. Thus, tumor heterogeneity and their associated difference in sensitivity to ROS-producing therapeutic agents must be considered in the design of PDT protocols for the prediction of its outcome. In this study, anticancer activity through ROS-mediated PDT using CPNs was compared in three GBM cell lines with different initial redox status. T98G cells were the most effective incorporating nanoparticles but also were the most resistant to CPN-PDT effect. In part, this feature could be attributed to the differential basal and PDT-induced antioxidant enzyme levels found in these cells measured by gene expression analysis. Furthermore, considering that cell-specific antioxidant enzyme status is a significant feature of GBM heterogeneity, establishing its correlation with CPN-PDT outcome might be important for designing novel and improved CPN-based treatments.

Assuntos

Glioblastoma/patologia , Nanomedicina/métodos , Nanopartículas , Fotoquimioterapia/métodos , Polímeros/química , Polímeros/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Humanos , Oxirredução , Espécies Reativas de Oxigênio/metabolismo

RESUMO

Aim: To assess monocyte-based delivery of conjugated polymer nanoparticles (CPNs) for improved photodynamic therapy (PDT) in glioblastoma (GBM). Materials & methods: Human monocyte cells (THP-1) and murine monocytes isolated from bone marrow (mBMDMs) were employed as stealth CPN carriers to penetrate into GBM spheroids and an orthotopic model of the tumor. The success of PDT, using this cell-mediated targeting strategy, was determined by its effect on the spheroids. Results: CPNs did not affect monocyte viability in the absence of light and did not show nonspecific release after cell loading. Activated monocytes incorporated CPNs in a higher proportion than monocytes in their naive state, without a loss of cellular functionality. In vitro PDT efficacy using cell-mediated delivery was superior to that using non vehiculized CPNs. Conclusion: CPN-loaded monocytes could efficiently deliver CPNs into GBM spheroids and the orthotopic model. Improved PDT in spheroids was confirmed using this delivery strategy.

Assuntos

Glioblastoma , Monócitos , Nanopartículas , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Camundongos , Polímeros/uso terapêutico

RESUMO

Photodynamic inactivation (PDI) protocols using photoactive metallated porphyrin-doped conjugated polymer nanoparticles (CPNs) and blue light were developed to eliminate multidrug-resistant pathogens. CPNs-PDI protocols using varying particle concentrations and irradiation doses were tested against nine pathogenic bacterial strains including antibiotic-resistant bacteria of the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens group. The bactericidal effect was achieved in methicillin-resistant Staphylococus aureus (S. aureus) strains using low light doses (9.6-14.4 J/cm2), while Gram-negative bacteria required a higher light dose (28.8 J/cm2). The bacteria-CPN interaction was studied through flow cytometry, taking advantage of the intrinsic CPN fluorescence, demonstrating that CPNs efficiently bind to the bacterial envelope. Finally, the performance of CPNs-PDI was explored in biofilms; good antibiofilm ability and almost complete eradication were observed for S. aureus and Escherichia coli biofilms, respectively, using confocal microscopy. Overall, we demonstrated that CPNs-PDI is an efficient tool not only to kill superbugs as sessile cells but also to disrupt and eradicate biofilms of highly relevant pathogenic bacterial species.

Assuntos

Nanopartículas , Porfirinas , Bactérias , Biofilmes , Plâncton , Polímeros , Porfirinas/farmacologia , Staphylococcus aureus

RESUMO

The use of conjugated polymer nanoparticles (CP NPs) of poly(9,9-dioctylfluorene-alt-benzothiadiazole) and poly(9,9-di-n-octylfluorenyl-2,7-diyl) as efficient photoinitiator systems (PIS) of vinyl polymerization in water is reported herein. CP NPs are biocompatible, excitable with blue commercial LEDs and, unlike visible light Type II PIS, do not need co-initiators to trigger a monomer chain reaction. CP NPs photoinitiate polymerization of a variety of acrylic monomers with initiation rates comparable to those observed for well-known Type II PIS. Given the extraordinarily large molar absorption coefficients of CP NPs (≈108 m-1 cm-1 ) very low particle concentration is required for effective polymerization. Additionally, CP NPs behave as conventional macrophotoinitiators significantly reducing contamination risks due to leaching of low molecular weight byproducts. These combined features make CP NPs PIS suitable to synthesize polymeric materials for many healthcare and biomedical applications including drug delivery, tissue engineering, prosthetic implants, and food/medicine packaging. These CP NPs PIS are also used to synthesize nano-hydrogels with a relatively narrow and controlled size distribution in the absence of surfactants. It is proposed that polymerization is initiated at the CP NPs surface by photogenerated free polarons, in close analogy to the mechanism previously described for PIS based on inorganic semiconductor NPs.

Assuntos

Luz , Nanopartículas/química , Polímeros/química , Compostos de Vinila/síntese química , Tamanho da Partícula , Polimerização , Solubilidade , Propriedades de Superfície , Compostos de Vinila/química , Água/química

RESUMO

The development of convenient synthetic methods and improved materials for the production of high load-capacity and biocompatible drug delivery systems is a challenging task with important implications in health sciences. In this work, acrylamide/2-hydroxyethylmethacrylate and N-isopropylacrylamide/2-hydroxyethylmethacrylate hydrogels were synthesized by photopolymerization using energy-efficient green-LEDs. A functionalized silsesquioxane was used as both crosslinker and co-initiator for the photopolymerization. The hybrid organic-inorganic nature of the silsesquioxane improved the resulting hydrogels' properties increasing their swelling capacity and biocompatibility. Additionally, the mild conditions used during the photopolymerization allowed the synthesis of hydrogels in the presence of antibiotics yielding high load-capacity materials in which the drug preserves its molecular structure and antimicrobial activity (as confirmed by HPLC and microbiological assays). The materials were characterized by FTIR, DSC and SEM. Additionally, the kinetics of gels´ swelling and drug release were studied under physiological conditions (pH 7.4 and 37 °C). The results demonstrate how hydrogel composition affects the antibiotics-release kinetics. The final drug release percentage increased with increasing molar fraction of acrylamide or N-isopropylacrylamide and in most cases exceeded 85%. Finally, the antibacterial effect of loaded gels was characterized using a number of assays against Gram negative and Gram positive bacteria. The observed antibacterial effect correlated well with swelling and drug release results. Furthermore, gels are not toxic for isolated erythrocytes as demonstrated by haemolytic tests. Overall, our results indicate that the produced hydrogels are promising materials to develop controlled drug-delivery devices such as capsules, dermatological patches and others.

Assuntos

Antibacterianos/farmacologia , Hidrogéis/química , Polimerização , Acrilamidas/química , Ampicilina/farmacologia , Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Gentamicinas/farmacologia , Hemólise/efeitos dos fármacos , Humanos , Hidrogéis/síntese química , Cinética , Metacrilatos/química , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Água

RESUMO

In this study, the phytoplankton structure of a freshwater reservoir located in central Argentina (Embalse Río Tercero) was analyzed using Beutler's method (Photosynthesis Research 72: 39-53, 2002), aiming to provide water quality control agencies with a reliable tool for early detection of algae blooms, particularly cyanobacteria. The method estimated the concentration of chlorophyll a (Chl a) contributed by individual algal groups in a real sample by fitting its fluorescence excitation spectrum to a linear combination of norm spectra of relevant algae groups. To this purpose, norm spectra for five algae genera usually found in Embalse Río Tercero, Microcystis, Chlorella, Cyclotella, Ceratium and Porphyridium, were constructed and posteriorly used to analyze samples collected in the reservoir in years 2014-2016. Results showed that the method worked well for the quick identification of the algae present in the samples, but it tended to overestimate its Chl a contents. This error was attributed to the large heterogeneity of the algal populations due to the aging of cells grown in environmental conditions.

RESUMO

AIM: Assess biocompatibility, uptake and photodynamic therapy (PDT) mechanism of metallated porphyrin doped conjugated polymer nanoparticles (CPNs) in human brain and colorectal tumor cells and macrophages. MATERIALS & METHODS: CPNs were developed employing 9,9-dioctylfluorene-alt-benzothiadiazole, an amphiphilic polymer (PS-PEG-COOH),  and platinum octaethylporphyrin. T98G, SW480 and RAW 264.7 cell lines were exposed to CPNs to assess uptake and intracellular localization. Additionally, a PDT protocol using CPNs was employed for the in vitro killing of cancer and macrophage cell lines. RESULTS & CONCLUSION: CPNs were well incorporated into glioblastoma and macrophage cells with localization in lysosomes. SW480 cells were less efficient incorporating CPNs with localization in the plasma membrane. In all cell lines PDT treatment was efficient inducing oxidative stress that triggered apoptosis.

Assuntos

Neoplasias Colorretais/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Porfirinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Humanos , Macrófagos/efeitos dos fármacos , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polímeros/química , Poliestirenos/química , Poliestirenos/farmacologia , Porfirinas/química , Células RAW 264.7

RESUMO

Conjugated polymer nanoparticles are widely used in fluorescent labeling and sensing, as they have mean radii between 5 and 100 nm, narrow size dispersion, high brightness, and are photochemically stable, allowing single particle detection with high spatial and temporal resolution. Highly crosslinked polymers formed by linking individual chains through covalent bonds yield high-strength rigid materials capable of withstanding dissolution by organic solvents. Hence, the combination of crosslinked polymers and conjugated polymers in a nanoparticulated material presents the possibility of interesting applications that require the combined properties of constituent polymers and nanosized dimension. In the present work, F8BT@pEGDMA nanoparticles composed of poly(ethylene glycol dimethacrylate) (pEGDMA; a crosslinked polymer) and containing the commercial conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) were synthesized and characterized. Microemulsion polymerization was applied to produce F8BT@pEDGMA particles with nanosized dimensions in a ∼25% yield. Photophysical and size distribution properties of F8BT@pEDGMA nanoparticles were evaluated by various methods, in particular single particle fluorescence microscopy techniques. The results demonstrate that the crosslinking/polymerization process imparts structural rigidity to the F8BT@pEDGMA particles by providing resistance against dissolution/disintegration in organic solvents. The synthesized fluorescent crosslinked nanoparticles contain (for the most part) single F8BT chains and can be detected at the single particle level, using fluorescence microscopy, which bodes well for their potential application as molecularly imprinted polymer fluorescent nanosensors with high spatial and temporal resolution.

RESUMO

Lithium diphenylphosphide unexpectedly provokes the ring-opening of tetrahydrofuran (THF) and by reaction with 3,6-dichloropyridazine leads to the formation of the ligand 3-chloro-6-(4-diphenylphosphinyl)butoxypyridazine (P⋯N), which was isolated. The reaction of this ligand with the (Re(CO)3(THF)Br)2 dimer yields the novel complex [Br(CO)3Re(µ-3-chloro-6-(4-diphenylphosphinyl)butoxypyridazine)2Re(CO)3Br] (BrRe(P⋯N)(N⋯P)ReBr), which was crystallized in the form of a chloroform solvate, (C46H40Br2Cl2N4O8P2Re2)·(CHCl3). The monoclinic crystal (P21/n) displays a bimetallic cage structure with a symmetry inversion centre in the middle of the rhenium to rhenium line. The molecule shows two oxidation signals occurring at +1.50 V and +1.76 V which were assigned to the ReI/ReII and ReII/ReIII metal-centered couples, respectively, while signals observed at -1.38 V and -1.68 V were assigned to ligand centered reductions. Experimental and DFT/TDDFT results indicate that the UV-Vis absorption maximum of BrRe(P⋯N)(N⋯P)ReBr occurring near 380 nm displays a metal to ligand charge transfer (MLCT) character, which is consistent with CV results. Upon excitation at this wavelength, a weak emission (Φem < 1 × 10-3) is observed around 580 nm (in dichloromethane) which decays with two distinct lifetimes τ1 and τ2 of 24 and 4.7 ns, respectively. The prevalence of non-radiative deactivation pathways is consistent with efficient internal conversion induced by the high conformational flexibility of the P⋯N ligand's long carbon chain. Measurements in a frozen solvent at 77 K, where vibrational deactivation is hindered, show intense emission associated with the 3MLCT state. These results demonstrate that BrRe(P⋯N)(N⋯P)ReBr preserves the dual emitting nature previously reported for the mononuclear complex RePNBr, with emission associated with and states.

RESUMO

We report herein a study on photoinduced electron transfer (eT) and energy transfer (ET) processes occurring between 9-methylanthracene-acrylate (A) and N,N-dimethylaniline-acrylate (D) derivatives incorporated into polymeric nanoparticles (NP). Five types of NPs were synthesized: PAD0, PAD25, PAD75, PD25, and PD75. All NPs are composed of a crosslinked polymer matrix of methyl methacrylate and ethylene glycol dimethacrylate. In addition, PAD0, PAD25 and PAD75 contain low doping levels of A. For PAD25 and PAD75, 25% and 75% of the mole fraction of methyl methacrylate is replaced by D, respectively. PD25 and PD75 were prepared as above but without A. NPs (diameter 6-9 nm) dispersed in organic solvents were characterized based on their UV-visible absorption, emission, excitation, and excitation anisotropy spectra and time dependent absorption and emission spectroscopy techniques. The emission decay profiles of A and D were always complex. Results indicate that A senses two distinct environments in all NPs. The emission quenching of PAD0 by DMA in DCM solutions is dynamic, and it is apparent that a significant fraction of A is inaccessible to the quencher. The emission of A is efficiently quenched by the presence of D in PAD25 and PAD75. The intra-NP photoinduced eT quenching mechanism has static and dynamic components. Selective excitation of D in PAD25 and PAD75 leads to the formation of the excited state of A via a singlet-singlet ET Föster type mechanism. Results indicate that both intra-NP eT and ET processes are more efficient in PAD75 due to the reduced average D*-A separation in these NPs.