Long-Term Outcomes of an International Cooperative Study of Intraoperative Radiotherapy Upfront Boost With Low Energy X-Rays in Breast Cancer.

Purpose: The purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort. Materials/Methods: Patients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors. Results: A total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12-180) months, and age was 58 (27-86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6-20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age <50 remained to be a significant prognostic factor for local recurrence (HR 0.19, 95% CI 0.08-0.47; p < 0.05). The 10-year estimated OS was 81.2%. Conclusion: Upfront boost with IORT yields similar local control outcomes to those EBRT-based reports. Results from prospective trials, regarding toxicity, cosmesis, and effectivity are awaited to confirm these findings.

[Quality of life and disease activity assessment in juvenile idiopathic arthritis]. / Evaluación de la calidad de vida y la actividad de la enfermedad en artritis idiopática juvenil.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatological disease in children. It is a multisystemic, dynamic pathophysiology of unknown cause and genetically heterogeneous. OBJECTIVE: To compare the quality of life and illness' activity in patients with juvenile idiopathic arthritis, from urban, suburban and rural areas. MATERIAL AND METHODS: Comparative, observational, and cross-sectional study in pediatric patients treated in a second-level medical care hospital, during the period from August to October 2015. The following questionnaires were applied: The Childhood Health Assessment Questionnaire for Quality of Life and The Disease Activity Score-28, in addition to the facial pain and verbal numerical scales for disease activity, both for patients and parents. The Kruskal-Wallis test was used for data analysis. RESULTS: 42 patients of three geostatistical areas were included: urban, suburban and rural; the middle age was 12.7 years, with predominance of the feminine sex (3:1). The polyarticulate type is more prevalent in the rural area. The pain is similar in the three regions. The population of the areas did not find significant difference for activity of the illness and quality of life between geostatistical areas (p ≤ 0.05). CONCLUSIONS: The patients with juvenile idiopathic arthritis are usually older of eight years. The quality of life is better in the patients of the urban area, compared to those of other areas.

INTRODUCCIÓN: la artritis idiopática juvenil (AIJ) es la enfermedad reumatológica crónica más frecuente en niños. Es una fisiopatología multisistémica, dinámica, de causa desconocida y genéticamente heterogénea. OBJETIVO: comparar la calidad de vida y la actividad de la enfermedad en pacientes con artritis idiopática juvenil, originarios de áreas urbanas, suburbanas y rurales. MATERIAL Y MÉTODOS: estudio comparativo, observacional y transversal, en pacientes pediátricos atendidos en un hospital de segundo nivel de atención médica, durante el periodo de agosto a octubre de 2015. Se aplicaron los cuestionarios: Childhood Health Assessment Questionnaire para calidad de vida y Disease Activity Score-28, además de las escalas facial del dolor y verbal numérica para actividad de la enfermedad, tanto a los pacientes como a los padres. Se utilizó la prueba de Kruskal-Wallis para el análisis de los datos. RESULTADOS: se incluyeron 42 pacientes de tres áreas geoestadísticas: urbana, suburbana y rural; la edad media fue de 12.7 años, con predominio del sexo femenino (3:1). El tipo de clasificación poliarticular es el más prevalente en el área rural. El dolor es similar en las tres regiones. No se encontró diferencia significativa para actividad de la enfermedad y calidad de vida entre la población de las áreas geoestadísticas (p ≤ 0.05). CONCLUSIONES: los pacientes con artritis idiopática juvenil suelen ser mayores de ocho años. La calidad de vida es mejor en los pacientes del área urbana, en comparación con los de las otras áreas.

Validation of coffee silverskin extract as a food ingredient by the analysis of cytotoxicity and genotoxicity.

The aim of the present study was to validate the food safety of CSE, by studying its effect on cytotoxicity (100-20000µg/ml) and genotoxicity (10, 100 and 1000µg/ml) and also to investigate its preventive potential (1, 10 and 100µg/ml) against B(a)P induced DNA damage. Prior to analyses, the antioxidant capacity and the microbiological quality of CSE were tested. DNA damage (strand breaks and oxidized purines/pyrimidines) was evaluated by the alkaline single-cell gel electrophoresis or comet assay. HepG2 cells were pre-treated with CSE (1, 10 and 100µg/ml) for 24h followed by the addition of 100µM B(a)P in presence of CSE for other 24h. Detection of oxidized purines and pyrimidines was carried out using Formamidopyrimidine DNA glycosylase or Endonuclease III enzymes, respectively. Chlorogenic acid (CGA), the major antioxidant present in coffee, was used as a control. Treatment with 100 µM B(a)P significantly increased (p<0.05) levels of DNA strand breaks and oxidized purine and pyrimidine bases. Treatment of HepG2 cells with CSE did not induce either cytotoxicity or genotoxicity. CSE significantly inhibited (p<0.05) genotoxicity induced by B(a)P and the observed effect may be associated to its antioxidant capacity. CGA alone at the concentration present in CSE was effective against B(a)P. Thus, CGA seems to be a contributor to the preventive effect of CSE against B(a)P induced DNA damage in HepG2 cells. In conclusion, CSE presents potential as a natural sustainable chemoprotective agent against the chemical carcinogen B(a)P.

Interactions of manufactured silver nanoparticles of different sizes with normal human dermal fibroblasts.

Silver compounds have been used for their medicinal properties for centuries. At present, silver nanoparticles (AgNPs) are reemerging as a viable topical treatment option for infections encountered in burns, open wounds and chronic ulcers. This study evaluated the in vitro mechanisms of two different sizes of AgNPs (4·7 and 42 nm) toxicity in normal human dermal fibroblasts. The toxicity was evaluated by observing cell viability and oxidative stress parameters. In all toxicity endpoints studied (MTT and lactate dehydrogenase assays), AgNPs of 4·7 nm were much more toxic than the large AgNPs (42 nm). The cytotoxicity of both AgNPs was greatly decreased by pre-treatment with the antioxidant N-acetyl-L-cysteine. The oxidative stress parameters showed significant increase in reactive oxygen species levels, depletion of glutathione level and slight, but not statistically significant inactivation of superoxide dismutase, suggesting generation of oxidative stress. Thus, AgNPs should be used with caution for the topical treatment of burns and wounds, medical devices etc, because their toxicity depends on the size, the smaller NPs being much more cytotoxic than the large.

In vivo genotoxicity assesment of silver nanoparticles of different sizes by the Somatic Mutation and Recombination Test (SMART) on Drosophila.

Silver nanoparticles (AgNPs) with antimicrobial activity are by far the most commercialized nano-compound. They are commonly used in medical products and devices, food storage materials, cosmetics and industrial products. Despite the increasing human exposure to AgNPs, they remain a controversial research area with regard to their toxic and genotoxic effects to biological systems. Although previous data have suggested that AgNPs induce toxicity in vitro, the in vivo studies on this topic are very limited. In the present study, the potential genotoxic activity of AgNPs of different sizes (4.7 and 42 nm) was evaluated using the in vivo Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. Larvae were treated with 25, 30 and 50 µg/ml of AgNPs 4.7 nm, and 250, 500 and 1000 µg/ml of AgNPs 42 nm. Data showed that AgNPs at the applied concentrations did not modify the spontaneous frequencies of spots indicating lack of mutagenic and recombinogenic activity. However, both AgNPs induced pigmentation defects and reduction in locomotor ability in adult flies. Therefore, further experiments must be carried out to gain a better understanding of the mechanism of action of AgNPs to ensure their safe use.

Effects of silver and gold nanoparticles of different sizes in human pulmonary fibroblasts.

Silver and gold nanoparticles (Ag-AuNPs) are currently some of the most manufactured nanomaterials. Accordingly, the hazards associated with human exposure to Ag-AuNPs should be investigated to facilitate the risk assessment process. In particular, because pulmonary exposure to Ag-AuNPs occurs during handling of these nanoparticles, it is necessary to evaluate the toxic response in pulmonary cells. The aim of this study was to evaluate the in vitro mechanisms of toxicity of different sizes of silver (4.7 and 42 nm) and gold nanoparticles (30, 50 and 90 nm) in human pulmonary fibroblasts (HPF). The toxicity was evaluated by observing cell viability and oxidative stress parameters. Data showed that AgNPs-induced cytotoxicity was size-dependent, whereas the AuNPs of the three sizes showed similar cytotoxicity. Silver nanoparticles of 4.7 nm were much more toxic than the large silver nanoparticles and the AuNPs. However, the pre-treatment with the antioxidant, N-acetyl-L-cysteine, protected HPF cells against treatment with Ag-AuNPs. The oxidative stress parameters revealed significant increase in reactive oxygen species levels, depletion of glutathione level and slight, but not statistically significant inactivation of superoxide dismutase, suggesting generation of oxidative stress. Hence, care has to be taken while processing and formulating the Ag-AuNPs till their final finished product.

Cytotoxicity and ROS production of manufactured silver nanoparticles of different sizes in hepatoma and leukemia cells.

Silver nanoparticles (AgNPs), which have well-known antimicrobial properties, are extensively used in various medical and general applications. In spite of the widespread use of AgNPs, relatively few studies have been undertaken to determine the cytotoxic effects of AgNPs. The aim of this study was investigate how AgNPs of different sizes (4.7 and 42 nm) interact with two different tumoral human cell lines (hepatoma [HepG2] and leukemia [HL-60]). In addition, glutathione depletion, inhibition of superoxide dismutase (SOD) and reactive oxygen species (ROS) generation were used to evaluate feasible mechanisms by which AgNPs exerted its toxicity. AgNPs of 4.7 nm and 42 nm exhibited a dramatic difference in cytotoxicity. Small AgNPs were much more cytotoxic than large AgNPs. A difference in the cellular response to AgNPs was found. HepG2 cells showed a higher sensitivity to the AgNPs than HL-60. However, the cytotoxicity induced by AgNPs was efficiently prevented by NAC treatment, which suggests that oxidative stress is primarily responsible for the cytotoxicity of AgNPs. Furthermore, cellular antioxidant status was disturbed: AgNPs exposure caused ROS production, glutathione depletion and slight, but not statistically significant inactivation of SOD.

Oxidative stress contributes to gold nanoparticle-induced cytotoxicity in human tumor cells.

Due to their exceptional properties, gold nanoparticles (AuNPs) have shown promising medical and technological applications in the treatment of cancer and the development of antimicrobial packaging and time-temperature indicators in the food sector. However, little is known about their cytotoxicity when they come into contact with biological systems. The aim of this work was to compare the effects of three commercially available AuNPs of different sizes (30, 50 and 90 nm) on human leukemia (HL-60) and hepatoma (HepG2) cell lines. AuNP-induced cytotoxicity was dose and time-dependent, with IC50 values higher than 15 µg/mL. Nanoparticle (NP) size and cell line slightly influenced on the cytotoxicity of AuNPs, although HL-60 cells proved to be more sensitive to the cytotoxic response than HepG2. N-Acetyl-L-cysteine (NAC) protected HL-60 and HepG2 cells only against treatment with 30 nm AuNPs. In both cell types, glutathione (GSH) content was drastically depleted after 72 h of incubation with the three AuNPs (less than 30% in all cases), while the reduction of superoxide dismutase activity (SOD) activity depended on cell line. HepG2, but not HL-60 cells, exhibited a decrease of SOD activity (∼ 45% of activity). The three AuNPs also caused a two-fold elevation of reactive oxygen species (ROS) production in both cell lines. Thus, protective effect of NAC, depletion of GSH and increase of ROS appear to be determined by NP size and indicate that oxidative stress contributes to cytotoxicity of AuNPs.

Nanopartículas de oro: aplicaciones y citotoxicidad in vitro / Gold nanoparticles: Applications and in vitro cytotoxicity

En los últimos años, la evolución en el desarrollo de productos elaborados a partir de nanotecnología ha experimentado un espectacular crecimiento. En particular, las nanopartículas de oro han despertado gran interés en los sectores biomédico y alimentario, donde se ha descrito su utilización en el tratamiento frente al cáncer o como parte integrante de envases resistentes a la abrasión, con propiedades antimicrobianas. Por tanto, se cree que la exposición humana a las nanopartículas de oro aumentará considerablemente en los próximos años, pudiendo tener esto repercusiones sobre la salud. En este marco, el estudio de la toxicología de las nanopartículas ha revelado que su toxicidad depende de multitud de factores. Además, en la bibliografía hay cierta controversia en torno a los posibles efectos citotóxicos inducidos por las nanopartículas de oro. Diversos estudios de exposición in vitro han destacado su inocuidad en algunas líneas celulares, mientras que otros trabajos demostraron respuesta citotóxica. La siguiente revisión tiene por objeto describir las propiedades más relevantes de las nanopartículas de oro considerando sus potenciales aplicaciones en medicina y en la industria de los alimentos, así como examinar su posible toxicidad, con especial énfasis en los estudios de citotoxicidad in vitro disponibles hasta el momento.

In the recent years, the development of nanotechnology-based products has experienced a spectacular growth. Especially, gold nanoparticles have awoken a great interest in the biomedical and food sector, where their applications in cancer treatment as well as their incorporation in abrasion resistant and antimicrobial packaging have been described. Therefore, it is believed that human exposure to gold nanoparticles will increase considerably in the next few years, which may arise possible human health hazards. Hence, toxicology studies on nanoparticles revealed that their toxicity depends on various factors. Furthermore, there is some controversy regarding to gold nanoparticle-induced cytotoxicity. Several in vitro studies have reported that gold nanoparticles are innocuous, while some investigations have demonstrated a cytotoxic response after the exposure to these. The aim of this review is to describe the most relevant properties of gold nanoparticles according to their possible applications in medicine and in food industry, as well as to provide information about their possible toxic effects, taking into account the cytotoxic in vitro studies published at present.

Nanopartículas de oro: aplicaciones y citotoxicidad in vitro / Gold nanoparticles: Applications and in vitro cytotoxicity

En los últimos años, la evolución en el desarrollo de productos elaborados a partir de nanotecnología ha experimentado un espectacular crecimiento. En particular, las nanopartículas de oro han despertado gran interés en los sectores biomédico y alimentario, donde se ha descrito su utilización en el tratamiento frente al cáncer o como parte integrante de envases resistentes a la abrasión, con propiedades antimicrobianas. Por tanto, se cree que la exposición humana a las nanopartículas de oro aumentará considerablemente en los próximos años, pudiendo tener esto repercusiones sobre la salud. En este marco, el estudio de la toxicología de las nanopartículas ha revelado que su toxicidad depende de multitud de factores. Además, en la bibliografía hay cierta controversia en torno a los posibles efectos citotóxicos inducidos por las nanopartículas de oro. Diversos estudios de exposición in vitro han destacado su inocuidad en algunas líneas celulares, mientras que otros trabajos demostraron respuesta citotóxica. La siguiente revisión tiene por objeto describir las propiedades más relevantes de las nanopartículas de oro considerando sus potenciales aplicaciones en medicina y en la industria de los alimentos, así como examinar su posible toxicidad, con especial énfasis en los estudios de citotoxicidad in vitro disponibles hasta el momento.(AU)

In the recent years, the development of nanotechnology-based products has experienced a spectacular growth. Especially, gold nanoparticles have awoken a great interest in the biomedical and food sector, where their applications in cancer treatment as well as their incorporation in abrasion resistant and antimicrobial packaging have been described. Therefore, it is believed that human exposure to gold nanoparticles will increase considerably in the next few years, which may arise possible human health hazards. Hence, toxicology studies on nanoparticles revealed that their toxicity depends on various factors. Furthermore, there is some controversy regarding to gold nanoparticle-induced cytotoxicity. Several in vitro studies have reported that gold nanoparticles are innocuous, while some investigations have demonstrated a cytotoxic response after the exposure to these. The aim of this review is to describe the most relevant properties of gold nanoparticles according to their possible applications in medicine and in food industry, as well as to provide information about their possible toxic effects, taking into account the cytotoxic in vitro studies published at present.(AU)

Efecto antiulceroso de una solucion viscosa oral a partir de un extracto de Bidens pilosa (Romerillo) en ratas / Antiulcerous affect of oral viscous solution from an extract of Bidens pilosa L. (romerillo) in rats

Se estudio el efecto antiulceroso de una forma farmaceutica, constituida por el residuo acuoso de un extracto hihdroalcoholico de Bidens pilosaL. en concentraciones de 40, 60 y 80 porciento en un vehiculo viscoso. La actividad de la preparacion se evaluo en tres modelos experimentales de lesiones gastricas en ratas inducidas por etanol, indometacina y estres por inmovilizacion a baja temperatura. Se emplearon tres grupos de animales que recibieron la solucion viscosa de Bidens pilosa por via oral durante 5 dias, en las tres concentraciones mencionadas, en dosis de 133,4; 212,1 y 282,8 mg de material vegetal/kg de peso, respectivamente. Un cuarto grupo se uso como control y recibio solamente vehiculo viscoso (placebo). Se obtuvo como resultado que la solucion viscosa de Bidens pilosa, en las tres concentraciones estudiadas, disminuyo significativamente el numero y la severidad de las lesiones de la mucosa gastrica inducidas por etanol y estres, pero no hubo proteccion contra el dano inducido por indometacina. La solucion viscosa que contenia extracto al 80 porciento fue la mas efectiva

Efecto antiulceroso de una solución viscosa oral a partir de un extracto de Bidens pilosa (Romerillo) en ratas / Antiulcerous affect of oral viscous solution from an extract of Bidens pilosa L. (romerillo) in rats

Se estudió el efecto antiulceroso de una forma farmacéutica, constituida por el residuo acuoso de un extracto hihdroalcohólico de Bidens pilosaL. en concentraciones de 40, 60 y 80 porciento en un vehículo viscoso. La actividad de la preparación se evaluó en tres modelos experimentales de lesiones gástricas en ratas inducidas por etanol, indometacina y estrés por inmovilización a baja temperatura. Se emplearon tres grupos de animales que recibieron la solución viscosa de Bidens pilosa por vía oral durante 5 días, en las tres concentraciones mencionadas, en dosis de 133,4; 212,1 y 282,8 mg de material vegetal/kg de peso, respectivamente. Un cuarto grupo se usó como control y recibió solamente vehículo viscoso (placebo). Se obtuvo como resultado que la solución viscosa de Bidens pilosa, en las tres concentraciones estudiadas, disminuyó significativamente el número y la severidad de las lesiones de la mucosa gástrica inducidas por etanol y estrés, pero no hubo protección contra el daño inducido por indometacina. La solución viscosa que contenía extracto al 80 porciento fue la más efectiva (AU)

Efectos de la zeolita sobre lesiones gástricas inducidas por etanolen ratas / Effects of zeolite on gastric lesions induced by ethanol in rats

Se estudió el efecto de una muestra de zeolita sobre la producción de lesiones en la mucosa gástrica de ratas inducidas por etanol y sobre la secreción ácido gástrico. La administración intragástrica de zeolita en dosis de 500 mg/kg produjo una disminución significativa del número y la severidad de las lesiones gástricas. La dosis de 100 mg/kg fue inefectiva. En el estudio de la secreción ácida gástirca se observó que la dosis de 500 mg/kg produjo un disminución significativa de la acidez y un ligero incremento de pH. La dosis de 100 mg/kg no indujo cambios en ninguna de las variables estudiadas. Concluimos que la zeolita en dosis de 500 mg/kg protegió la mucosa gástrica de las ratas frente al daño inducido por el etanol y esta protección puede estar relacionada en parte con el efecto neutralizador del ácido en el lumen gástrico

Valoración de la actividad antiulcerosa de varias plantas medicinales I / Pharmacological screening of the antiulcerative activity of several medicinal plants. I

Se determinó la utilidad de un grupo de plantas medicinales en la terapéutica de la úlcera gastroduodenal, mediante la evaluación de su acción protectora sobre las lesiones de la mucosa gástrica inducidas por estrés por inmovilización y frío en ratas. Se evaluaron 11 especies (Piper-aduncum, Cymbopogon titratus, Ocimun sanctum, Stachyrpheta jamaicensis, Plantago major, Justicia pectoralis, Psidium gujava, Cajanus indicus, Pseudelephantopus spicatus, ipomea tuba y Lawsonia inermis). Solamente con Piper aduncum y Pseudelephantopus spicatus se encontró una disminución significativa del número y la severidad de las lesiones gástricas. En los casos de Stachytarpheta jamaicensis y Psidium guajava, por el contrario. se observó un incremento significativo de ambas variables, por lo que se puede inferir que en las decocciones de estas plantas pudieran existir componentes que lesionen o potencien el desarrollo de lesiones de la mucosa gástrica

Efectos de la zeolita sobre lesiones gástricas inducidas por etanolen ratas / Effects of zeolite on gastric lesions induced by ethanol in rats

Se estudió el efecto de una muestra de zeolita sobre la producción de lesiones en la mucosa gástrica de ratas inducidas por etanol y sobre la secreción ácido gástrico. La administración intragástrica de zeolita en dosis de 500 mg/kg produjo una disminución significativa del número y la severidad de las lesiones gástricas. La dosis de 100 mg/kg fue inefectiva. En el estudio de la secreción ácida gástirca se observó que la dosis de 500 mg/kg produjo un disminución significativa de la acidez y un ligero incremento de pH. La dosis de 100 mg/kg no indujo cambios en ninguna de las variables estudiadas. Concluimos que la zeolita en dosis de 500 mg/kg protegió la mucosa gástrica de las ratas frente al daño inducido por el etanol y esta protección puede estar relacionada en parte con el efecto neutralizador del ácido en el lumen gástrico