Gold Half-Shell-Coated Paclitaxel-Loaded PLGA Nanoparticles for the Targeted Chemo-Photothermal Treatment of Cancer.

Conventional cancer therapies suffer from nonspecificity, drug resistance, and a poor bioavailability, which trigger severe side effects. To overcome these disadvantages, in this study, we designed and evaluated the in vitro potential of paclitaxel-loaded, PLGA-gold, half-shell nanoparticles (PTX-PLGA/Au-HS NPs) conjugated with cyclo(Arg-Gly-Asp-Phe-Lys) (cyRGDfk) as a targeted chemo-photothermal therapy system in HeLa and MDA-MB-231 cancer cells. A TEM analysis confirmed the successful gold half-shell structure formation. High-performance liquid chromatography showed an encapsulation efficiency of the paclitaxel inside nanoparticles of more than 90%. In the release study, an initial burst release of about 20% in the first 24 h was observed, followed by a sustained drug release for a period as long as 10 days, reaching values of about 92% and 49% for NPs with and without near infrared laser irradiation. In in vitro cell internalization studies, targeted nanoparticles showed a higher accumulation than nontargeted nanoparticles, possibly through a specific interaction of the cyRGDfk with their homologous receptors, the ανß3 y ανß5 integrins on the cell surface. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, reducing the cell viability to 23% for the HeLa cells and 31% for the MDA-MB-231 cells. Thus, our results indicate that these multifuncional nanoparticles can be considered to be a promising targeted chemo-photothermal therapy system against cancer.

Gold Nanorods with Mesoporous Silica Shell: A Promising Platform for Cisplatin Delivery.

The versatile combination of metal nanoparticles with chemotherapy agents makes designing multifunctional drug delivery systems attractive. In this work, we reported cisplatin's encapsulation and release profile using a mesoporous silica-coated gold nanorods system. Gold nanorods were synthesized by an acidic seed-mediated method in the presence of cetyltrimethylammonium bromide surfactant, and the silica-coated state was obtained by modified Stöber method. The silica shell was modified first with 3-aminopropyltriethoxysilane and then with succinic anhydride to obtain carboxylates groups to improve cisplatin encapsulation. Gold nanorods with an aspect ratio of 3.2 and silica shell thickness of 14.74 nm were obtained, and infrared spectroscopy and ζ potential studies corroborated surface modification with carboxylates groups. On the other hand, cisplatin was encapsulated under optimal conditions with an efficiency of ~58%, and it was released in a controlled manner over 96 h. Furthermore, acidic pH promoted a faster release of 72% cisplatin encapsulated compared to 51% in neutral pH.

Apendicetomía electiva: caso clínico y revisión de la bibliografía / Elective appendectomy: clinical case and literature review / Apendectomia eletiva: caso clínico e revisão da literatura

Las masas inflamatorias de origen apendicular son cuadros de presentación poco frecuente, el 3 % de las apendicitis agudas. Su manejo terapéutico puede ser sistematizado en cirugía de inicio o tratamiento conservador. Este último consiste en antibioticoterapia exclusiva, o asociada al drenaje percutáneo. Es una alternativa frente a emprender una apendicectomía demandante, con riesgo de no identificar el apéndice cecal, lesión visceral y necesidad de conversión o resecciones extendidas. Sin embargo, en estos pacientes, la ausencia de la confirmación diagnóstica anatomo-patológica obliga a un seguimiento protocolizado a fin de descartar diagnósticos diferenciales de mayor relevancia pronóstica. Objetivo: Presentar el caso de un paciente en el que se realizó manejo conservador y apendicetomía electiva. Se realizó una revisión bibliográfica de las pautas de seguimiento e indicación de la apendicectomía electiva. Discusión y conclusiones: Las masas inflamatorias de origen apendicular representan un desafío diagnóstico y terapéutico, requiriendo un manejo y seguimiento específico. La indicación de apendicectomía electiva es controversial, es planteable frente a la persistencia de imágenes patológicas y dudas diagnósticas, o en pacientes con apendicitis recurrentes.

Inflammatory masses of appendiceal origin are infrequent; represent 3 % of acute appendicitis. Its therapeutic management can be systematized in initial surgery or conservative treatment. The latter consists of exclusive antibiotic therapy, or associated with percutaneous drainage. it is an alternative to undertaking a demanding appendectomy, with the risk of not identifying the cecal appendix, visceral injury, and the need for conversion or extended resections. However, the absence of pathological diagnostic confirmation requires protocolized follow-up in order to rule out differential diagnoses of greater prognostic relevance. Objective: present the case of a patient who underwent conservative management and elective appendectomy. a bibliographic review was carried out in the databases: pubmed, cochrane library, scielo and lilacs. Discussion and conclusions: inflammatory masses of appendiceal origin represent a diagnostic and therapeutic challenge, requiring specific management and follow-up. The indication for elective appendectomy is controversial, it is considered in the presence of persistent pathological images and diagnostic doubts, or in patients with recurrent appendicitis.

Massas inflamatórias de origem apendicular são quadros de apresentação pouco frequentes, 3 % de as apendicites agudas. seu manejo terapêutico pode ser sistematizado em cirurgia inicial ou tratamento conservador. esta última consiste na antibioticoterapia exclusiva, ou associada à drenagem percutânea. é uma alternativa à realização de uma apendicectomia exigente, com risco de não identificação do apêndice cecal, lesão visceral e necessidade de conversão ou ressecções extensas. no entanto, nesses pacientes, a ausência de confirmação diagnóstica patológica requer acompanhamento protocolarizado para afastar diagnósticos diferenciais de maior relevância prognóstica. Objetivo: apresentar o caso de um paciente submetido a tratamento conservador e apendicectomia eletiva. foi realizada revisão bibliográfica nas bases de dados: pubmed, biblioteca cochrane, scielo e lilacs. Discussão e conclusões: as massas inflamatórias de origem apendicular representam um desafio diagnóstico e terapêutico, exigindo manejo e seguimento específicos. a indicação de apendicectomia eletiva é controversa, sendo considerada na presença de imagens patológicas persistentes e dúvidas diagnósticas, ou em pacientes com apendicite recorrente.

Opciones terapéuticas para la colecistitis aguda: de las guías de Tokio 2018 a la práctica clínica / Therapeutic options for acute cholecystitis: from the Tokyo guidelines 2018 to clinical practice / Opções terapêuticas para colecistite aguda: das diretrizes de Tóquio 2018 à prática clínica

Resumen: Introducción: el tratamiento "gold standard" de la colecistitis aguda es la colecistectomía laparoscópica temprana. En pacientes añosos de alto riesgo anestésico-quirúrgico, con cuadros de evolución subaguda y/o con repercusión sistémica, es alternativa el tratamiento médico exclusivo o asociado al drenaje vesicular percutáneo. Objetivo: analizar y comparar las recomendaciones internacionales con las conductas terapéuticas en dos centros asistenciales de tercer nivel para pacientes con colecistitis aguda. Método: trabajo descriptivo, prospectivo de 161 pacientes con colecistitis aguda litiásica asistidos en los departamentos de emergencia del Hospital de Clínicas y el Hospital Español entre mayo de 2018 y mayo de 2019. Resultados: la colecistectomía laparoscópica temprana fue indicada en el 88% de los pacientes, con 3% de conversión y 9% de morbilidad. 12% recibieron manejo no operatorio, asociándose en el 65% colecistostomía percutánea. La edad avanzada, comorbilidades, discrasias y la severidad del cuadro presentaron asociación significativa con la modalidad terapéutica (p <0,05). El 40% de los pacientes en los que se realizó manejo no operatorio presentó recurrencias sintomáticas. A todos se les realizó la colecistectomía en diferido. Conclusiones: la colecistectomía laparoscópica temprana es la conducta terapéutica más frecuente. Las principales indicaciones de manejo no operatorio en nuestro medio son las características sistémicas desfavorables. El mismo presenta altas tasas de éxito y escasa morbilidad con una recurrencia sintomática del 40%.

Abstract: Introduction: early laparoscopic cholecystectomy is the gold standard treatment for acute cholecystitis. However, exclusive medical treatment (EMC) or medical treatment associated with percutaneous gallbladder drainage is the treatment of choice in elderly patients given their high surgical and anesthetic risk and upon the subacute course of the condition and/or its systemic repercussions. Objective: to analyze and compare international guidelines to the therapeutic behavior for patients with acute cholecystectomy in two third-level hospitals. Methodology: descriptive, prospective study of 161 patients with litiasic acute cholecystitis treated in the ER of Hospital de Clínicas and Hospital Español between May 2018 and May 2019. Results: early laparoscopic cholecystectomy was indicated in 88% of patients, conversion being 3% and morbidity 9%. Twelve percent of patients received non-surgical treatment, 65% of which evidenced percutaneous cholecystostomy. Old age, comorbidities, dyscrasias, and severity of the condition were closely related to the therapeutic modality (p < 0.05). Forty percent of patients who received non-surgical treatment presented symptomatic repercussions. They all underwent delayed cholecystectomy. Conclusions: early laparoscopic cholecystectomy is the most frequent treatment of choice. Unfavorable systemic characteristics are the main indications for non-surgical management in our country. This surgical treatment evidences high success rates and scarce morbidity with 40% of systemic repercussions.

Resumo: Introdução: o tratamento padrão ouro da colecistite aguda é a colecistectomia laparoscópica precoce. Em pacientes idosos com alto risco anestésico-cirúrgico, com evolução subaguda e/ou repercussão sistêmica, o tratamento clínico isolado ou associado à drenagem percutânea da vesícula biliar é uma alternativa. Objetivo: analisar e comparar recomendações internacionais com condutas terapêuticas em dois centros terciários para pacientes com colecistite aguda. Método: estudo descritivo e prospectivo de 161 pacientes com colecistite aguda de cálculos atendidos nos serviços de emergência do Hospital de Clínicas e Hospital Español no período maio de 2018 - maio de 2019. Resultados: a colecistectomia laparoscópica precoce foi indicada em 88% dos pacientes, com 3% de conversão e 9% de morbidade. 12% receberam tratamento não operatório, associado a 65% colecistostomia percutânea. Idade avançada, comorbidades, discrasias e gravidade do quadro apresentaram associação significativa com a modalidade terapêutica (p < 0,05). 40% dos pacientes nos quais o manejo não operatório foi realizado apresentaram recidivas sintomáticas. Todos foram submetidos à colecistectomia diferida. Conclusões: a colecistectomia laparoscópica precoce é a abordagem terapêutica mais frequente. As principais indicações para o manejo não operatório em nosso meio são as características sistêmicas desfavoráveis. Apresentando altas taxas de sucesso e baixa morbidade com recorrência sintomática de 40%.

Técnica TAPP en manos jóvenes. Es posible reproducir los resultados de la técnica Lichtenstein para la hernia inguinal sintomática primaria unilateral / Tapp technique performed by young hands. Reproducing the results of the lichtenstein procedure for symptomatic primary unilateral inguinal hernia

RESUMEN Antecedentes: La hernioplastia inguinal es el procedimiento quirúrgico más frecuentemente realizado dentro de la Cirugía General. Se realizan anualmente 20 millones de hernioplastias; la técnica de Lichtenstein y la transabdominal preperitoneal (TAPP) mediante cirugía laparoscópica son las más utilzadas. Objetivo: El objetivo del presente estudio es valorar la factibilidad de la realización del TAPP, en un centro universitario, por parte de residentes y cirujanos jóvenes en formación. Se comparó dicho procedimiento con la técnica de Lichtenstein valorando los resultados en los primeros 30 días del posoperatorio. Las principales variables para estudiar fueron: complicaciones, dolor posoperatorio, estadía hospitalaria y costo del procedimiento. Como variables para estudiar, a largo plazo, se compararon la recidiva herniaria y el dolor crónico. Material y métodos: Se realizó un estudio observacional comparando dos técnicas quirúrgicas utilizando la base de datos del Servicio con información adquirida de forma prospectiva. Se analizaron 80 pacientes, divididos en dos grupos: hernioplastia de Lichtenstein (grupo1) y hernioplastia por TAPP (grupo 2), durante el período comprendido desde mayo de 2015 hasta mayo de 2019, en dos Centros Universitarios de Montevideo Uruguay (Hospital de Clínicas y Hospital Español). Resultados: No hubo diferencia significativa en la estadía hospitalaria y complicaciones posoperatorias. El grupo del Lichtenstein presentó una recidiva herniaria. La hernioplastia laparoscópica presentó un tiempo operatorio promedio de 20 minutos más y el costo de materiales fue mayor. Si bien el dolor posoperatorio en las primeras 24 horas fue mayor en TAPP, el dolor a las 48 horas, 7días, un mes, tres meses y seis meses fue similar en ambos grupos. Conclusión: La técnica de TAPP, para la hernia inguinal primaria unilateral, es factible de ser realizada por cirujanos jóvenes o en formación, con un porcentaje de complicaciones, dolor posoperatorio y recidivas similares al Lichtenstein, aunque con un costo de materiales y tiempo operatorio levemente mayor.

ABSTRACT Background: Inguinal hernia repair is one of the most common procedures in general surgery. Each year, 20 million surgeries for inguinal hernia repaired are performed; the most common techniques used are the Lichtenstein procedure and the transabdominal preperitoneal (TAPP) laparoscopic approach. Objective: The aim of the present study is to evaluate the outcomes of the TAPP approach performed by residents and young surgeons in training in a university center. TAPP was compared with the Lichtenstein and the outcomes at 30 days were compared. The variables considered were complications, postoperative pain, length of hospital stay and procedure-related costs. The long-term variables analyzed were recurrence and chronic pain. Material and methods: We conducted an observational study comparing two surgical techniques, using prospectively acquired information from the database of our department. The cohort was made up of 80 patients undergoing inguinal hernia repair in two university-based hospitals in Montevideo, Uruguay (Hospital de Clínicas and Hospital Español), between May 2015 and May 2019. The patients were divided into two groups: Lichtenstein procedure (group 1) and TAPP procedure (group 2). Results: There were no significant differences in length of hospital stay and postoperative complications. One patient in the Lichtenstein group presented hernia recurrence. Mean operative time was 20 minutes longer with laparoscopic hernia repair, and the cost of the materials was higher. Postoperative pain at 24 hours was greater in the TAPP group, but was similar at 48 hours, 7 days, one month, three months and six months in both groups. Conclusion: The use of TAPP technique for unilateral primary inguinal hernia is feasible to perform by young surgeons or surgeons in training, and the percentage of complications, postoperative pain and recurrences is similar to that of the Lichtenstein technique, although the cost of materials and operative time are slightly higher.

Chitosan Functionalized with 2-Methylpyridine Cross-Linker Cellulose to Adsorb Pb(II) from Water.

In this study, chitosan was chemically modified with 2-methylpyridine. Subsequently, the modified chitosan was cross-linked to cellulose using succinic anhydride. Additionally, the capacity of cellulose derivatives to adsorb Pb(II) ions in an aqueous solution was studied through the determination of Pb(II) ions concentration in water, using microwave plasma atomic emission spectroscopy (MP-AES). A maximum adsorption capacity of 6.62, 43.14, 60.6, and 80.26 mg/g was found for cellulose, cellulose-succinic acid, cellulose-chitosan, and cellulose-chitosan-pyridine, respectively. The kinetic data analysis of the adsorption process showed a pseudo-second-order behavior. The increase in metal removal from water is possibly due to metal chelation with the carbonyl group of succinic acid, and the pyridine groups incorporated into chitosan.

Impacto de la pandemia COVID-19 en la formación del residente de cirugía general en un servicio universitario / Impact of the covid-19 pandemic on the training of general surgery residents in a university hospital / Impacto da pandemia de COVID-19 na formação de residentes de cirurgia geral em um serviço universitário

Resumen: Introducción: a nivel mundial, la pandemia COVID-19 determinó una disminución significativa en el volumen de cirugía electiva. Existe preocupación por parte de generaciones de residentes quirúrgicos debido a las consecuencias en su formación. Si bien la formación alcanza otros aspectos que exceden a la práctica quirúrgica, ésta no deja de ser un pilar fundamental. Objetivo: cuantificar el impacto de la pandemia COVID-19 en el volumen asistencial de los residentes de cirugía general en un servicio universitario. Método: es un estudio observacional, retrospectivo y analítico. Se comparó el volumen quirúrgico y asistencial de los residentes de cirugía general durante el período entre el 13/03/2020 y el 13/12/2020, posterior al inicio de la pandemia COVID-19, con el volumen registrado en el mismo período previo al inicio de la pandemia. Resultados: todos los residentes participaron en un menor número de cirugías. El mayor impacto fue en la participación de cirugías de coordinación, siendo menores las diferencias en la cirugía de urgencia. El mayor impacto en cuanto a volumen de pacientes operados fue para el residente de primer año. Discusión y conclusiones: a nivel mundial, la pandemia determinó una notoria disminución en el volumen de cirugías electivas. Este trabajo demostró una disminución significativa en el volumen quirúrgico asistencial del residente de cirugía general, por lo que, de prolongarse las medidas sanitarias, sería sustancial evaluar la necesidad de proyectar objetivos e instancias alternativas de aprendizaje.

Summary: Introduction: the COVID-19 pandemic caused a meaningful reduction in the number of elective surgeries at the global level. There is a great concern among different generations of surgical residents, on the consequences this might have on their medical training. Despite the medical training includes other aspects beyond the surgical practice, surgeries constitute an essential foundation. Objective: to quantify the impact of the COVID-19 pandemic on the number of surgeries where the general surgery residents participated, in a university hospital. Method: observational, retrospective and analytical study where the number of surgeries and assistance by the general surgery residents between March 13, 2020 and December 13, 2020, after the outbreak of the COVID-19 pandemic was compared to the number of surgeries recorded during the same period of time prior to the pandemic. Results: all the residents participated in a smaller number of surgeries. The greater impact was found in their participation in elective surgeries, while the difference in number was smaller in emergency surgeries. The greater impact in terms of number of patients operated involved first year residents. Discussion and conclusions: globally, the pandemic caused a significant reduction in the number of elective surgeries. This study demonstrated an important decrease in the number of assisted surgeries for the general surgery residents. Therefore, if the health emergency measures were extended, it would be important to evaluate the need to set goals and alternative forms of learning.

Resumo: Introdução: em todo o mundo, a pandemia de COVID-19 determinou uma redução significativa na quantidade de cirurgias eletivas. Há preocupação por parte de gerações de residentes cirúrgicos pelas consequências em sua formação. Embora o treinamento alcance outros aspectos que vão além da prática cirúrgica, esta ainda é um pilar fundamental. Objetivo: quantificar o impacto da pandemia COVID-19 na quantidade de atendimento de residentes de cirurgia geral em um serviço universitário. Método: estudo observacional, retrospectivo e analítico. A quantidade de cirurgias e de cuidados dos residentes de cirurgia geral no período de 13/03/2020 a 13/12/2020, após o início da pandemia de COVID-19, foi comparado com a quantidade registrada em um período similar anterior à pandemia. Resultados: todos os residentes participaram de menos cirurgias. O maior impacto foi na participação de cirurgias de coordenação, sendo menores as diferenças nas cirurgias de emergência. O maior impacto em termos de quantidade de pacientes operados foi para o residente do primeiro ano. Discussão e conclusões: em todo o mundo, a pandemia determinou uma diminuição acentuada na quantidade de cirurgias eletivas. Este trabalho demonstrou uma diminuição significativa na quantidade da atenção cirúrgica do residente de cirurgia geral; se as medidas de saúde forem prolongadas, seria fundamental avaliar a necessidade de se projetar objetivos e instâncias alternativas de aprendizagem.

Improving Cell Penetration of Gold Nanorods by Using an Amphipathic Arginine Rich Peptide.

INTRODUCTION: Gold nanorods are highly reactive, have a large surface-to-volume ratio, and can be functionalized with biomolecules. Gold nanorods can absorb infrared electromagnetic radiation, which is subsequently dispersed as local heat. Gold nanoparticles can be used as powerful tools for the diagnosis and therapy of different diseases. To improve the biological barrier permeation of nanoparticles with low cytotoxicity, in this study, we conjugated gold nanorods with cell-penetrating peptides (oligoarginines) and with the amphipathic peptide CLPFFD. METHODS: We studied the interaction of the functionalized gold nanorods with biological membrane models (liposomes) by dynamic light scattering, transmission electron microscopy and the Langmuir balance. Furthermore, we evaluated the effects on cell viability and permeability with an MTS assay and TEM. RESULTS AND DISCUSSION: The interaction study by DLS, the Langmuir balance and cryo-TEM support that GNR-Arg7CLPFFD enhances the interactions between GNRs and biological membranes. In addition, cells treated with GNR-Arg7CLPFFD internalized 80% more nanoparticles than cells treated with GNR alone and did not induce cell damage. CONCLUSION: Our results indicate that incorporation of an amphipathic sequence into oligoarginines for the functionalization of gold nanorods enhances biological membrane nanoparticle interactions and nanoparticle cell permeability with respect to nanorods functionalized with oligoarginine. Overall, functionalized gold nanorods with amphipathic arginine rich peptides might be candidates for improving drug delivery by facilitating biological barrier permeation.

Cosecha ganglionar en cáncer de colon. Mitos y magia / Lymph node harvest in colon cancer. Myths and magic / Contagem de linfonodos no câncer de cólon. Mitos e magia

Resumen: El compromiso ganglionar es crítico en la estadificación del cáncer de colon como factor pronóstico y como determinante de tratamiento adyuvante. Se sigue discutiendo el número de ganglios adecuados a resecar, cuáles son los factores que inciden en la cosecha ganglionar y el significado biológico de ésta. Se revisan las variables clínicas y de la propia biología tumoral que hacen que la definición de un número determinado de ganglios, como gold standard de cosecha ganglionar adecuada, sea controversial. El número 12 no necesariamente es un número "mágico" marcador de calidad. Extender la resección para aumentar la cosecha ganglionar no mejora la estadificación, expone al paciente a riesgos innecesarios, sin efecto terapéutico comprobado. La "magia" sigue siendo realizar resecciones regladas, que incluyan el pedículo vascular y el meso satélite al tumor, ajustando la resección a las características del paciente. Menos no es más, pero más no es necesariamente mejor.

Summary: Lymph node compromise is critical in colon cancer staging, as a prognostic factor and to determine adjuvant therapy. The number of lymph nodes to be resected is still under discussion, as well as the factor that have an impact on lymph node harvest and its biological significance. We reviewed clinical variables and variables that are specific to the tumor, what results in the definition of a certain number of lymph nodes, as the adequate Gold Standard for lymph node harvest being controversial. 12 is not necessarily a "magic" number that marks quality. Extending resection to increase lymph node harvest does not improve staging, it exposes patients to unnecessary risks, there being no therapeutic effect guaranteed. The "Magic" continues to be routine resection that includes the cystic pedicle and the area around the tumour, adjusting resection to the patient's characteristics. Less is not best, but more is not necessarily better.

Resumo: O compromisso ganglionar é crítico no estadiamento do câncer de cólon, como fator prognóstico e como determinante do tratamento adjuvante. A discussão sobre o número de gânglios adequados a ressecar, quais são os fatores que incidem sobre a definição do número de linfonodos a ser retirados e seu significado biológico. Faz-se uma revisão das variáveis clínicas e da própria biologia tumoral, que fazem com que a definição de um número determinado de gânglios como Gold Standard do número adequado de linfonodos a remover seja controversa. O número 12 não é necessariamente um número "mágico", um marcador de qualidade. Ampliar a ressecção para aumentar o número de linfonodos que serão retirados não melhora o estadiamento, expõe o paciente a riscos desnecessários, sem um efeito terapêutico comprovado. A "Magia" continua sendo realizar ressecções de acordo com parâmetros definidos, que incluam o pedículo vascular e o mesocólon satélite ao tumor, ajustando a ressecção às características do paciente. Menos não é mais, porém mais não é necessariamente melhor.

Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy.

The conventional treatment (cytoreduction combined with cisplatin/carboplatin and taxane drugs) of ovarian cancer has a high rate of failure and recurrence despite a favorable initial response. This lack of success is usually attributed to the development of multidrug resistance mechanisms by cancer cells and avoidance of the anti-growth effects of monoclonal targeted therapeutic antibodies. The disease, like other cancers, is characterized by the overexpression of molecular markers, including HER2 receptors. Preclinical and clinical studies with trastuzumab, a HER2-targeted therapeutic antibody, reveal a low improvement of the outcomes of HER2 positive ovarian cancer patients. Therefore, here, we propose a cisplatin-loaded, HER2 targeted poly(lactic-co-glycolic) nanoplatform, a system capable to escape the drug-efflux effect and to take advantage of the overexpressed HER2 receptors, using them as docks for targeted chemotherapy. The NP/trastuzumab ratio was determined after fluorescein labeling of antibodies and quantification of fluorescence in NPs. The system was also characterized in terms of size, zeta potential, drug release kinetics, cytotoxicity and cellular internalization in the epithelial ovarian cancer cell line SKOV-3, and compared with the HER2 negative breast cancer cell line HCC70. Our results show an increased cytotoxicity of NPs as compared to free cisplatin, and moreover, an enhanced internalization and cytotoxicity due to the bionfunctionalization of NPs with the monoclonal antibody.

Cirugía del día: colecistectomía laparoscópica. ¿Es factible en nuestro medio? / Laparoscopic cholecystectomy as an ambulatory surgical procedure. Is it feasible in our context?

Introducción: la colecistectomía laparoscópica es la cirugía mayor más frecuente en Uruguay. Su baja morbimortalidad y rápida recuperación han llevado a incluirla en programas de cirugía del día. Objetivo: evaluar la factibilidad de la inclusión de la colecistectomía laparoscópica en un programa de cirugía del día en nuestros hospitales públicos. Material y método: estudio cooperativo (Hospital de Clínicas, Hospital Español y Hospital Central de las Fuerzas Armadas) observacional descriptivo y retrospectivo de pacientes en que se practicó una colecistectomía laparoscópica (CIE-9-mc 51.23) como cirugía del día entre junio de 2011 y junio de 2015. Se consideró cirugía del día una estancia igual o menor a 12 horas. Criterios de inclusión: ASA I/II, domicilio en área urbana con adecuada contención, teléfono y transporte particular. Exclusión: pacientes con colecistitis, diagnóstico preoperatorio de coledocolitiasis, eventos anestésicos-quirúrgicos adversos. Se recabaron datos demográficos, incidentes y complicaciones de la cirugía, evolución posoperatoria a 30 días. Resultados: se reclutó un total de 32 pacientes (rango etario: 17-66 años), 26 de sexo femenino. En 30 pacientes se practicó la colecistectomía laparoscópica con un alta hospitalaria entre las 6 y 12 horas del posoperatorio. Dos pacientes que aceptaron participar en el programa acusaron dolor parietal posoperatorio que impidió un alta precoz y fueron excluidos. En un paciente se diagnosticó una coledocolitiasis en la colangiografía intraoperatoria y se realizó una coledocolitotomía trancística sin incidentes y se mantuvo dentro del protocolo. No hubo pacientes excluidos por incidentes o accidentes intraoperatorios. No se registró morbilidad posoperatoria en los controles programados en policlínica a la semana y a los 30 días del posoperatorio. Ningún paciente tuvo síntomas que motivaran consulta en servicio de urgencias durante ese lapso. Conclusiones: los resultados de esta experiencia parecen demostrar que la colecistectomía laparoscópica en régimen de cirugía del día es aplicable en nuestros servicios públicos en forma eficiente y segura. Señalamos la importancia de una rigurosa selección de pacientes subrayando el ingreso voluntario al programa, adecuado nivel de comprensión del procedimiento y sus riesgos, disponer de facilidades (soporte domiciliario y acceso al centro asistencial), supeditando el egreso en el día a la ausencia de eventos que demanden prolongar la observación posoperatoria.

Abstract Introduction: laparoscopic cholecystectomy is the most frequent major surgery in Uruguay. Given its low morbimortality rates and fast recovery it has been included in an ambulatory surgical procedures program. Objective: to assess feasibility of including laparoscopic cholecystectomy in an ambulatory surgical procedures program in public hospitals in Uruguay. Method: multi-center (University Hospital, Español Hospital and the Armed Forces Central Hospital), cooperative, descriptive and retrospective study of patients who underwent laparoscopic cholecystectomy (CIE-9-mc 51.23) as an ambulatory surgery between June, 2012 and June, 2015. Ambulatory surgery was defined as that which implied hospital stays equal to or lower than 12 hours. Inclusion criteria: ASA I, II, living in an urban area with the appropriate support network, telephone and private means of transport available. Exclusion criteria: patients with choledocholithiasis, history of negative surgical events due to anesthesia. Demographic data were collected, as well as surgery incidents and complications and postoperative surgery upon 30 days. Results: 32 patients were recruited (age ranged between 17 and 66 years old), 26 of them were female. Laparoscopic cholecystectomy was performed in 30 patients, and patients were discharged between 6 to 12 hours after the postoperative. Two patients who accepted to participate in the program referred postoperative parietal pain which prevented them from an early discharge and were excluded. One patient was diagnosed with choledocholithiasis in the intraoperative cholangiography and a transcystic choledocholithotomy was performed with no complications, acting within the protocol. No patients were excluded as a result of intraoperative incidents or accidents. No postoperative morbility was recorded in the programed follow up at the policlinic one week after surgery and 30 days after the postoperative. No patient felt symptoms that caused consultation at the emergency room during the above mentioned period of time. Conclusions: the results of this experience seem to prove that laparoscopic cholecystectomy in ambulatory surgery is applicable to our public services in an effective and safe way. We point out the importance of a rigorous selection of patients and emphasize on the fact that is advisable for patients to voluntary enter the program, and they need for understand well the procedure and its risks. Also, facilities must be available for home support and access to health care centers, and discharge on the day the surgery is performed will depend on the absence of events that indicate the need for a longer postoperative observation.

Resumo Introdução: a colecistectomia laparoscópica é a cirurgia maior mais frequente no Uruguai. Com baixa morbimortalidade e rápida recuperação fizeram com que fosse incluída nos programas de cirurgia ambulatoria. Objetivo: avaliar a viabilidade da inclusão da colecistectomia laparoscópica em um programa de cirurgia ambulatória nos hospitais públicos. Material e método: estudo cooperativo (Hospital de Clínicas, Hospital Español e Hospital Central de las Fuerzas Armadas) observacional descritivo e retrospectivo de pacientes nos quais foi realizada uma colecistectomia laparoscópica (CIE-9-mc 51.23) como cirurgia ambulatoria no periodo junho de 2011 - junho de 2015. Foi considerada como cirurgia ambulatória a permanência igual ou menor que 12 horas. Critérios de inclusão: ASA I/II, domicilio em área urbana com apoio adequado, telefone e transporte particular. Exclusão: pacientes com coleciste, diagnóstico pré-operatório de coledocolitiase, eventos anestésicos-cirúrgicos adversos. Foram coletados dados demográficos, incidentes e complicações da cirurgia e evolução pós-operatória aos 30 dias. Resultados: foram incluídos 32 pacientes (idades entre 17 e 66 anos), sendo 26 de sexo feminino. Em 30 pacientes foi realizada uma colecistectomia laparoscópica com alta hospitalar depois de 6 e 12 horas do procedimento. Dois pacientes que aceitaram participar no programa informaram dor parietal pós-operatória que impediu a alta precoce e foram excluídos. Em um paciente foi diagnosticada uma coledocolitiase na colangiografia intra-operatória e foi realizada uma coledocolitotomia trancística sem incidentes e foi mantido no protocolo. Não foram excluídos pacientes por incidentes ou acidentes intra-operatórios. Não se observou morbidade pós-operatória nos controles programados no ambulatório depois de uma semana e de 30 dias do procedimento. Nenhum paciente apresentou sintomas que motivaram consulta en serviço de urgências durante esse período. Conclusões: os resultados desta experiência parecem demonstrar que a colecistectomia laparoscópica en regime de cirurgia ambulatoria é aplicável nos nossos serviços públicos de maneira eficiente e segura. Destacamos a importância de seleção rigorosa dos pacientes destacando o ingresso voluntario ao programa, um nível adequado de compreensão do procedimento e seus riscos, dispor de facilidades (apoio domiciliar e acesso ao centro assistencial), condicionando a alta no dia à ausência de eventos que demandem uma observaçao pós-operatória mais prolongada.

Oligomers, protofibrils and amyloid fibrils from recombinant human lysozyme (rHL): fibrillation process and cytotoxicity evaluation for ARPE-19 cell line.

Amyloid-associated diseases, such Alzheimer's, Huntington's, Parkinson's, and type II diabetes, are related to protein misfolding and aggregation. Herein, the time evolution of scattered light intensity, hydrophobic properties, and conformational changes during fibrillation processes of rHL solutions at 55 °C and pH 2.0 were used to monitor the aggregation process of recombinant human lysozyme (rHL). Dynamic light scattering (DLS), thioflavin T (ThT) fluorescence, and surface tension (ST) at the air-water interface were used to analyze the hydrophobic properties of pre-amyloid aggregates involved in the fibrillation process of rHL to find a correlation between the hydrophobic character of oligomers, protofibrils and amyloid aggregates with the gain in cross-ß-sheet structure, depending on the increase in the incubation periods. The ability of the different aggregates of rHL isolated during the fibrillation process to be adsorbed at the air-water interface can provide important information about the hydrophobic properties of the protein, which can be related to changes in the secondary structure of rHL, resulting in cytotoxic or non-cytotoxic species. Thus, we evaluated the cytotoxic effect of oligomers, protofibrils and amyloid fibrils on the cell line ARPE-19 using the MTT reduction test. The more cytotoxic protein species arose after a 600-min incubation time, suggesting that the hydrophobic character of pre-amyloid fibrils, in addition to the high prevalence of the cross-ß-sheet conformation, can become toxic for the cell line ARPE-19.

Interaction and cytotoxic effects of hydrophobized chitosan nanoparticles on MDA-MB-231, HeLa and Arpe-19 cell lines.

In this work, we investigate the effect of chitosan hydrophobization on the internalization and cytotoxic effect of chitosan-based nanoparticles (NPs) on breast cancer cells (MDA-MB-231), cervical cancer cells (HeLa) and noncancer cells (Arpe-19). We also analyzed the interaction of NPs with a phospholipid (DPPC) membrane model at the airwater interface. An alkylation procedure to insert 8 carbon chains along the chitosan macromolecule with final 10 and 30 % substitution degrees was used. Nuclear magnetic resonance (NMR) and infrared spectroscopes (IR) were used to evaluate the success and extent of the hydrophobization procedure. Size, shape, and charge of NPs were evaluated by dynamic light scattering (DLS), atomic force microscope (AFM), and zeta potential, respectively. The effect of hydrophobicity on NPs was the reduction of the NPs average size, the formation of slightly elongated structures and the enhancing of the interaction of NPs with a DPPC monolayer at the air-water interface. By using fluorescence images on fluorescein-chitosan NPs, we observed a higher internalization of hydrophobic chitosan NPs in cancer cells in comparison with a low internalization of these NPs in normal cells. Even when non modified chitosan NPs were highly internalized in all cell lines, hydrophobized chitosan NPs showed a significantly higher cytotoxic effect on cancer cells in comparison with a lower effect showed by non-modified chitosan NPs on these cells. The cytotoxic effect on the normal cell line used was low for native chitosan NPs and negligible for hydrophobized chitosan NPs.