Melanoma metastásico en intestino delgado: causa infrecuente de perforación: reporte de caso / Metastatic melanoma in the small intestine: infrequent cause of perforation: case report / Melanoma metastático em intestino delgado: causa rara de perfuração: relato de caso

El intestino delgado es el sitio de asiento más frecuente del melanoma metastásico. Su diagnóstico es un desafío por cursar asintomático o con síntomas inespecíficos. Son pocos los casos que presentan complicaciones, siendo infrecuente la peritonitis por perforación. El objetivo del trabajo es comunicar el caso clínico de una peritonitis por perforación de una metástasis de melanoma en intestino delgado. Caso clínico: Paciente de sexo masculino de 66 años con diagnóstico de melanoma de cuello y secundario óseo, encefálico y pulmonar, fue intervenido de urgencia por peritonitis aguda por perforación de metástasis en intestino delgado. El estudio histológico confirmó secundarismo de melanoma cutáneo. Conclusión: Sabiendo que el yeyuno íleon es el sitio de asiento más frecuente de las metástasis de melanoma, ante la presencia de síntomas digestivos inespecíficos o anemia se debe sospechar su compromiso y evaluar posibles alternativas terapéuticas.

The small intestine is the most frequent site of metastatic melanoma. However, its diagnosis continues to be a challenge since it is usually asymptomatic or with non-specific symptoms. Few cases result in complications, peritonitis due to perforation being infrequent. The objective of the work is to report a clinical case of peritonitis due to perforation of a melanoma metastasis in the small intestine. Clinical case: A 66-year-old male patient diagnosed with melanoma of the neck and secondary bone, brain and lung melanoma, underwent emergency surgery for acute peritonitis due to perforation of metastasis in the small intestine, which was resected and anastomosed. The histology confirmed the secondary nature of the cutaneous melanoma. Conclusion: Knowing that the jejunum-ileum is the most frequent site of melanoma metastases, in the presence of non-specific digestive symptoms or anemia, its involvement should be suspected and possible therapeutic alternatives should be evaluated.

O intestino delgado é o local mais frequente de melanoma metastático. O diagnóstico é um desafio por ser assintomático ou apresentar sintomas inespecíficos. Há poucos casos que apresentam complicações, sendo pouco frequente a peritonite por perfuração. O objetivo deste trabalho é relatar um caso clínico de peritonite por perfuração de metástase de melanoma no intestino delgado. Caso clínico: Paciente do sexo masculino, 66 anos, diagnosticado com melanoma no pescoço com metástase óssea, cefálica e pulmonar. Foi submetido a cirurgia de emergência por peritonite aguda por perfuração de metástases do intestino delgado. O estudo histológico confirmou melanoma cutâneo. Conclusão: Sabendo que o jejuno e o íleo é o local mais frequente de metástase de melanoma, na presença de sintomas digestivos inespecíficos ou anemia deve-se suspeitar de seu acometimento e avaliar possíveis alternativas terapêuticas.

Características clínicas de pacientes pediátricos con síndrome de dificultad respiratoria aguda asociado con COVID-19 / Clinical characteristics of pediatric patients with acute respiratory distress syndrome due to COVID-19

Resumen Introducción: Existen pocos reportes de síndrome de dificultad respiratoria aguda (SDRA) con COVID-19 en pacientes pediátricos. El objetivo de este estudio fue describir las características de los pacientes pediátricos críticamente enfermos con COVID-19, la frecuencia del SDRA, la mecánica ventilatoria y los resultados de la posición prona. Métodos: Se llevó a cabo un estudio retrospectivo y observacional de los pacientes ingresados del 1 de abril al 30 de septiembre de 2020. Resultados: Ingresaron 34 pacientes a la unidad de terapia intensiva pediátrica (UTIP) con prueba positiva para SARS-CoV-2. De ellos, 13 presentaron SDRA, 11 requirieron ventilación mecánica invasiva y siete fueron pronados como estrategia de oxigenación. Todos los pacientes clasificados como SDRA graves fueron pronados. La obesidad fue la comorbilidad más importante. Las complicaciones asociadas con SDRA fueron el síndrome inflamatorio multisistémico (p < 0.05) y la lesión renal aguda (p < 0.05). La procalcitonina fue mayor en los pacientes con SDRA, al igual que los días de estancia en la UTIP (p < 0.05). El éxito de la maniobra de pronación se alcanzó 8 horas después.Los resultados observados fueron los siguientes relación presión arterial de oxígeno/fracción inspirada de oxígeno 128 vs. 204, índice de oxigenación 8.9 vs. 5.9, distensibilidad pulmonar estática 0.54 vs. 0.70 ml/cmH2O/kg, y presión meseta 24 vs. 19 cmH2O (p < 0.05). El uso de narcóticos fue mayor en el grupo de SDRA más pronación que en los no pronados (124 vs. 27 h; p < 0.01). La mortalidad asociada con SARS-CoV-2 fue del 5.8%. Conclusiones: El SDRA se presentó en el 38.2% de los niños admitidos a UTIP, y con mayor frecuencia en los pacientes con obesidad. La maniobra de pronación aplicada en los casos severos, mejoró la oxigenación de la mécanica pulmonar. Ninguno de los pacientes falleció por SDRA.

Abstract Background: There are only a few reports of acute respiratory distress syndrome (ARDS) in patients with SARS-CoV-2 in pediatrics. This study aimed to describe the characteristics of critically ill pediatric patients with COVID-19, the frequency of ARDS, ventilatory mechanics and results of prone position. Methods: We conducted a retrospective, observational study of patients admitted to the pediatric intensive care unit (PICU) between April 1 to September 30, 2020. Results: Thirty-four patients were admitted to pediatric intensive care unit, 31.7% were SARS-CoV-2 positive. 13 presented ARDS, 11 required invasive mechanical ventilation, and seven were pronated as an oxygenation strategy. All patients classified as severe ARDS were pronated. Obesity was the most important comorbidity. The complications associated with ARDS were multisystemic inflammatory syndrome (8 vs. 4; p < 0.05) and acute kidney injury (8 vs. 3; p < 0.05). Procalcitonin was higher in patients with ARDS, as were the days of stay in PICU (p < 0.05). The success of the pronation maneuver was achieved 8 hours later , with the following results: arterial oxygen partial pressure to fractional inspired oxygen ratio 128 vs. 204, oxygenation index 8.9 vs. 5.9, static lung compliance 0.54 vs. 0.70 ml/cmH2O/kg, plateau pressure 24 vs. 19 cmH2O (p < 0.05). The use of narcotics was higher in the group with ARDS plus pronation 124 vs. 27 hours in the non-pronated (p < 0.01). Mortality associated with SARS-CoV-2 was 5.8%. Conclusions: ARDS was presented in 38.2% of the children admitted to PICU and was more frequent in obese patients. Pronation, performed in severe cases, improved oxygenation and lung mechanics indexes. No patient died of ARDS.

Genistein Activates Transcription Factor EB and Corrects Niemann-Pick C Phenotype.

Niemann-Pick type C disease (NPCD) is a lysosomal storage disease (LSD) characterized by abnormal cholesterol accumulation in lysosomes, impaired autophagy flux, and lysosomal dysfunction. The activation of transcription factor EB (TFEB), a master lysosomal function regulator, reduces the accumulation of lysosomal substrates in LSDs where the degradative capacity of the cells is compromised. Genistein can pass the blood-brain barrier and activate TFEB. Hence, we investigated the effect of TFEB activation by genistein toward correcting the NPC phenotype. We show that genistein promotes TFEB translocation to the nucleus in HeLa TFEB-GFP, Huh7, and SHSY-5Y cells treated with U18666A and NPC1 patient fibroblasts. Genistein treatment improved lysosomal protein expression and autophagic flux, decreasing p62 levels and increasing those of the LC3-II in NPC1 patient fibroblasts. Genistein induced an increase in ß-hexosaminidase activity in the culture media of NPC1 patient fibroblasts, suggesting an increase in lysosomal exocytosis, which correlated with a decrease in cholesterol accumulation after filipin staining, including cells treated with U18666A and NPC1 patient fibroblasts. These results support that genistein-mediated TFEB activation corrects pathological phenotypes in NPC models and substantiates the need for further studies on this isoflavonoid as a potential therapeutic agent to treat NPCD and other LSDs with neurological compromise.

Effectiveness of a multicomponent treatment versus conventional treatment in patients with fibromyalgia: Study protocol.

BACKGROUND: Fibromyalgia (FM) is a chronic pain syndrome characterized by widespread musculoskeletal pain and multiple symptoms. It is a common clinical condition whose etiology is unclear. Currently, there is no gold standard treatment for FM. Management of this condition is therefore aimed at reducing symptoms and maintaining the individual's ability to function optimally. Based on the principal symptoms and characteristics of individuals with FM, we hypothesized that the implementation of a multicomponent treatment (with physical exercise, cognitive behavioral therapy adding to a graded motor imagery program, and therapeutic neuroscience education) would be more effective than conventional treatment in women with FM. This paper describes the rationale and methods of study intended to test the effectiveness of multicomponent treatment versus conventional treatment in patients with FM. METHOD/DESIGN: Fifty-six female individuals between 18 and 65 years of age, who were referred to the physical therapy department of the Rehabilitar Center in Chile, will be randomized into two treatment arms. The intervention group will receive a multicomponent treatment program for duration of 12 weeks. The control group will receive a conventional treatment for this condition for 12 weeks. The primary outcome measure will be the pain intensity score, measured by the numeric pain rating scale (NPRS), and the secondary outcomes will be the FM Impact Questionnaire (FIQ), and affective components of pain, such as catastrophizing using the Pain Catastrophizing Scale (PCS), fear of movement using the Tampa Scale Kinesiophobia (TSK), and sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI). DISCUSSION: This paper reports the design of a randomized clinical trial aimed at assessing the effectiveness of the multicomponent treatment versus conventional treatment in women with FM. TRIAL REGISTRATION: Brazilian registry of clinical trials UTN number U1111-1232-0862. Registered 22 April 2019.

7-epi-Clusianone, a Multi-Targeting Natural Product with Potential Chemotherapeutic, Immune-Modulating, and Anti-Angiogenic Properties.

Targeted therapies have changed the treatment of cancer, giving new hope to many patients in recent years. The shortcomings of targeted therapies including acquired resistance, limited susceptible patients, high cost, and high toxicities, have led to the necessity of combining these therapies with other targeted or chemotherapeutic treatments. Natural products are uniquely capable of synergizing with targeted and non-targeted anticancer regimens due to their ability to affect multiple cellular pathways simultaneously. Compounds which provide an additive effect to the often combined immune therapies and cytotoxic chemotherapies, are exceedingly rare. These compounds would however provide a strengthening bridge between the two treatment modalities, increasing their effectiveness and improving patient prognoses. In this study, 7-epi-clusianone was investigated for its anticancer properties. While previous studies have suggested clusianone and its conformational isomers, including 7-epi-clusianone, are chemotherapeutic, few cancer types have been demonstrated to exhibit sensitivity to these compounds and little is known about the mechanism. In this study, 7-epi-clusianone was shown to inhibit the growth of 60 cancer cell types and induce significant cell death in 25 cancer cell lines, while simultaneously modulating the immune system, inhibiting angiogenesis, and inhibiting cancer cell invasion, making it a promising lead compound for cancer drug discovery.

Endosalpingiosis de cicatriz operatoria de Pfannenstiel: reporte de caso / Endosalpingiosis of Pfannenstiel incision scar: a case report

Introducción: la endosalpingiosis es una enfermedad benigna caracterizada por el crecimiento ectópico del epitelio de la trompa de Falopio, siendo su presencia en cicatrices operatorias excepcional, habiéndose reportado cuatro casos en la literatura internacional. Caso clínico: se presenta el caso de una paciente de 40 años que consultó por dolor sobre incisión de Pfannenstiel y tumoración a dicho nivel. La misma se resecó y el estudio anatomopatológico informó endosalpingiosis. Discusión: el diagnóstico de endosalpingiosis cutánea es posoperatorio y realizado luego del estudio de la pieza de resección. Con su extirpación completa, se resuelve definitivamente la sintomatología y en los pocos casos publicados en la literatura no se ha reportado recidiva.

Introducion: endosalpingiosis is a benign disease characterized by the ectopic growth of the epithelium in the Fallopian tube, being it exceptional in surgical scars, four cases having been reported by international literature. Clinical case: the study presents the clinical case of a 40 year old female patient who consulted for pain in the Pfannenstiel incision and a tumour on the site. After resection, pathological study revealed endosalpingiosis. Discussion: the diagnosis of cutaneous endosalpingiosis occurs after surgery and upon the analysis of the resected piece. Complete removal results in the final solution of symptoms and no relapse has been reported in cases published in literature.

Introdução: a endossalpingiose é uma condição benigna que se caracteriza pelo crescimento ectópico do epitélio da trompa de Falópio; sua presença em cicatrizes operatórias é excepcional sendo que somente quatro casos foram encontrados na literatura internacional. Caso clínico: apresenta-se o caso clínico de uma paciente de 40 anos de sexo feminino que consultou por dor e tumoração na incisão de Pfannenstiel. O laudo de anatomia patológico da tumoração ressecada foi endossalpingiose. Discussão: o diagnóstico de endossalpingiose cutânea é pós-operatório e é feito pelo exame da peça de ressecção. Sua extirpação completa soluciona definitivamente a sintomatologia; os poucos casos publicados na literatura não informam recidivas.

Nicotinamide Augments the Anti-Inflammatory Properties of Resveratrol through PARP1 Activation.

Resveratrol (RSV) and nicotinamide (NAM) have garnered considerable attention due to their anti-inflammatory and anti-aging properties. NAM is a transient inhibitor of class III histone deacetylase SIRTs (silent mating type information regulation 2 homologs) and SIRT1 is an inhibitor of poly-ADP-ribose polymerase-1 (PARP1). The debate on the relationship between RSV and SIRT1 has precluded the use of RSV as a therapeutic drug. Recent work demonstrated that RSV facilitates tyrosyl-tRNA synthetase (TyrRS)-dependent activation of PARP1. Moreover, treatment with NAM is sufficient to facilitate the nuclear localization of TyrRS that activates PARP1. RSV and NAM have emerged as potent agonists of PARP1 through inhibition of SIRT1. In this study, we evaluated the effects of RSV and NAM on pro-inflammatory macrophages. Our results demonstrate that treatment with either RSV or NAM attenuates the expression of pro-inflammatory markers. Strikingly, the combination of RSV with NAM, exerts additive effects on PARP1 activation. Consistently, treatment with PARP1 inhibitor antagonized the anti-inflammatory effect of both RSV and NAM. For the first time, we report the ability of NAM to augment PARP1 activation, induced by RSV, and its associated anti-inflammatory effects mediated through the induction of BCL6 with the concomitant down regulation of COX-2.

Evaluación del nivel de participación del nutricionista en la prescripción dietética en hospitales públicos y privados de Chile / Evaluation of Clinical Dietitian Participation in Adequate Prescription of Dietary Indications in Public and Private Hospitals in Chile

Antecedentes: actualmente, Chile tiene un déficit de dietistas clínicos y se desconoce si este déficit está afectando la prescripción de indicaciones dietéticas adecuadas para pacientes hospitalizados. Objetivo: evaluar el nivel de participación del nutricionista clínico en la prescripción dietética en los hospitales públicos y privados del territorio nacional, entre los meses de agosto y octubre del año 2016. Materiales y métodos: estudio exploratorio, descriptivo; se invitaron a participar a 360 nutricionistas, contestaron 110 nutricionistas clínicos. Se aplicó un cuestionario de 21 preguntas, enviado vía correo electrónico. Resultados: las horas diarias dedicadas al servicio clínico presentaron una mediana de 6 horas, el 41,8 % de los encuestados tenía entre 26 y 50 pacientes a su cargo. El 99 % de los nutricionistas puede sugerir cambios en la prescripción dietética; sin embargo, un 45 % de las sugerencias realizadas al médico para modificar regímenes son registradas siempre en la ficha clínica. La participación en la prescripción dietética al inicio del tratamiento corresponde a un 9,1 %, en la evolución es de un 32,7 % y en la prescripción realizada al alta es de un 56,4 %. A más años de experiencia y más horas dedicadas al servicio se presenta un significativo mejor puntaje en la prescripción dietética (p<0,05). Conclusiones: el nivel de participación del nutricionista clínico es medio, los nutricionistas con más años de experiencia y mayor número de horas dedicadas a los pacientes presentan mayor prescripción dietética.

Background: Currently Chile has a deficit of clinical dietitians and it is unknown if this deficit is affecting the prescription of adequate dietary indications to hospital patients. Objective: Evaluate the participation level of clinical dietitians in the adequate prescription of dietary indications in public and private hospitals nationally, between August and November 2016. Materials and Methods: Exploratory descriptive study. 360 dietitians were invited to participate, and 110 accepted. A 21-question self-response questionnaire was sent to participants via email. Results: Daily hours dedicated to clinical services was a median of 6 hours among participants, 41.8% of whom had between 26 and 50 patients in their care. 99% of the dietitians are able to suggest changes to the dietary prescriptions; however only 45% of the modifications that are suggested to the doctors are ever recorded in the clinical records. Participation in dietary prescription at the beginning of patient treatment is 9.1 %, throughout the hospital stay is 32.7 %, and prescriptions made at discharge correspond to 56.4 %. More years of experience and more hours dedicated to clinical service correspond to a significantly better percentage in dietary prescriptions administered (p<0.05). Conclusions: The level of dietitian participation is average; the dietitians with more years of experience and higher number of hours dedicated to patient care present better dietary prescription to hospital patients.

Necrotizing fasciitis of the neck and head complicated with chronic osteomyelitis: Case report presentation.

INTRODUCTION: Necrotizing fasciitis (NF) is a severe infectious condition associated with significant morbidity and mortality and characteristically has a higher incidence in adults; pediatric cases are very rare. In this case report we describe, the clinical presentation, management and outcome of a patient with necrotizing fasciitis of the neck and head complicated with chronic osteomyelitis. PRESENTATION OF THE CASE: An 18 month-old, latin, male, diagnosed with rickets and Crouzon syndrome, twenty-four hours post- craniofacial remodeling surgery presented tissue edema, indurated skin and violaceous and well delimited lesions in the neck and head. The patient developed septic shock, acute osteomyelitis and infection of the cranial grafts. Multiple surgical lavages, debridation of the necrotic tissue and resection of the affected bone, in combination with multiple antibiotics, laboratory test methods, VAC therapy and hyperbaric oxygen were required for successful treatment and full recovery of the patient. DISCUSSION: Although early antibiotic therapy and critical care are basic for the treatment of patients with NF, early aggressive surgical treatment is crucial for an adequate outcome. Adjuvant treatment for NF such as the Vacuum-assisted closure and the hyperbaric oxygen therapy are very useful to accelerate wound healing. Moreover, special laboratory test methods such as the checkerboard can be used to determine the adequate antimicrobial combination of drugs in the case of multi resistant organisms. CONCLUSIONS: Early diagnosis, adequate antibiotic therapy and aggressive surgical debridement of the necrotic tissue combined with VAC and hyperbaric oxygen therapy played an important role in the successful treatment of NF.

Immunohistochemical staining patterns of alpha-keratins in normal tissues from two reptile species: implications for characterization of squamous cell carcinomas.

BACKGROUND: Cytokeratins with epitopes in common with those of alpha (acidic and basic) mammalian keratins have been immunohistochemically demonstrated in the epidermis of reptiles. However, there are no reports of immunohistochemical staining patterns of alpha-keratins in other tissues from reptiles. Because the epithelial tumours usually retain the keratin patterns of their normal epithelial origin, it is necessary to know in advance these patterns in the major normal epithelia and organs. We used anti-alpha human keratin AE1 and AE3 monoclonal antibodies to study the staining patterns of alpha-keratins in the major normal epithelia and organs from two reptile species [the bearded dragon (Pogona vitticeps) and the loggerhead sea turtle (Caretta caretta)]. We also studied the immunolocalization of alpha-keratins in squamous cell carcinomas (SCCs) in a bearded dragon and two loggerhead turtles. RESULTS: Acidic alpha-keratin (AE1 positive) was detected in many of the epithelial tissues of the bearded dragons; however, the detection of basic alpha-keratin (AE3 positive) was much more limited. Alpha-keratins were detected in a greater number of tissues of loggerhead turtles compared with those observed in bearded dragons. In the bearded dragon SCC, all layers of the nests of neoplastic cells, including the cornified layer of the keratin pearls, were strongly reactive with the AE1 antibody. However, a weak reactivity using the AE3 antibody was detected in the basal and intermediate layers of these nests. In the cutaneous SCCs of both sea turtles, acidic alpha-keratin was detected in the basal and suprabasal layers, and in all of the invasive neoplastic cords, while basic alpha-keratin was mainly detected in the invasive neoplastic cords. The pattern observed in the metastases in both turtles consisted of immunohistological detection of acidic alpha-keratin in all metastatic foci, and limited or lack of detection of basic alpha-keratin. CONCLUSIONS: This study provides, for the first time, information about the immunohistochemical staining patterns of alpha-keratins in normal tissues from bearded dragons and loggerhead sea turtles, and confirms the usefulness of AE1 and AE3 monoclonal antibodies in these reptile species. The use of these antibodies also contributed to a better characterization of SCCs in these species.

Percepciones corporales en trabajadoras sexuales / Body perceptions in female sexual workers / Percepções corporales em trabalhadoras sexuais

Resumen En Chile existe un déficit de información respecto a la vida de las trabajadoras sexuales, lo que ha implicado una barrera para la comprensión y formulación de medidas de salud que respondan de manera efectiva a sus necesidades. El objetivo de esta investigación es comprender la percepción de cuerpo de las trabajadoras sexuales en Santiago, para contribuir en la atención de salud y en la orientación de la gestión del cuidado de Enfermería desde las percepciones que las trabajadoras presentan en torno a su cuerpo y a su experiencia con él. Para esto se desarrolló un estudio de tipo cualitativo, con enfoque teórico-metodológico de Teoría Fundamentada, utilizando entrevistas en profundidad como técnica de recolección de datos, las cuales fueron analizadas hasta la codificación abierta. Se pudo determinar que las participantes relacionan su percepción corporal asociada al cuerpo físico, realizando acciones de autocuidado orientadas a la mantención, higiene y seguridad física de éste; sin embargo, la percepción se manifiesta también mediante la influencia de la construcción social en torno al cuerpo de la trabajadora sexual, generando efectos tanto en su visión del trabajo sexual como en las experiencias asociadas en torno a su práctica.

Abstract In Chile there is a lack of information regarding the lives of sexual workers, which has imposed a barrier to the understanding and formulation of health policies that respond effectively to their needs. The objective of this research is to understand the self perception of the body of the female sexual workers in Santiago, in order to contribute to the health care and orientation of the management of Nursing care from the perceptions that they present around their body and their experience with it. A qualitative study was developed, with a theoretical-methodological approach based theory, using in-depth interviews as a technique of data collection, which were analyzed using open coding. It was possible to determine that the participants relate their body perception associated to the physical body, performing self-care actions oriented to the maintenance, hygiene and physical security of the body. However, perception is also manifested through the influence of social construction around the body of the sexual worker, generating effects both in her vision of sexual work and in the experiences associated with her practice.

Resumo Em Chile existe um déficit de informação com respeito à vida das trabalhadoras sexuais, o que tem implicado uma barreira para o entendimento e formulação de medidas de saúde que respondam de maneira efetiva a suas necessidades. O objectivo desta investigação é compreender a percepção de corpo das trabalhadoras sexuais em Santiago, para contribuir na atenção de saúde e na orientação da gestão do cuidado de Enfermaria, desde as percepções as trabalhadoras apresentam em torno de seu corpo e a sua experiência com ele. Para isto se desenvolveu um estudo de tipo qualitativo, com enfoque teórico-metodológico de Teoria Fundamentada, utilizando entrevistas em profundidade como técnica de coleta de dados, as quais foram analisadas até a codificação aberta. Pôde-se determinar que as participantes relacionam sua percepção corporal sócia ao corpo físico, realizando acções de autocuidado orientadas à mantención, higiene e segurança física deste no entanto, a percepção manifesta-se também mediante a influência da construção social em torno do corpo da trabalhadora sexual, gerando efeitos tanto em sua visão do trabalho sexual como nas experiências associadas em torno de sua pratica.

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds.

Tissue engineering offers a promising strategy to restore injuries resulting from trauma, infection, tumor resection, or other diseases. In spite of significant progress, the field faces a significant bottleneck; the critical need to understand and exploit the interdependencies of tissue healing, angiogenesis, and inflammation. Inherently, the balance of these interacting processes is affected by a number of injury site conditions that represent a departure from physiological environment, including reduced pH, increased concentration of free radicals, hypoglycemia, and hypoxia. Efforts to harness the potential of immune response as a therapeutic strategy to promote tissue repair have led to identification of natural compounds with significant anti-inflammatory properties. This article provides a concise review of the body's inflammatory response to biomaterials and describes the role of oxygen as a physiological cue in this process. We proceed to highlight the potential of natural compounds to mediate inflammatory response and improve host-graft integration. Herein, we discuss the use of natural compounds to map signaling molecules and checkpoints that regulate the cross-linkage of immune response and skeletal repair.

Reduction of Blood Amyloid-ß Oligomers in Alzheimer's Disease Transgenic Mice by c-Abl Kinase Inhibition.

One of the pathological hallmarks of Alzheimer's disease (AD) is the presence of amyloid plaques, which are deposits of misfolded and aggregated amyloid-beta peptide (Aß). The role of the c-Abl tyrosine kinase in Aß-mediated neurodegeneration has been previously reported. Here, we investigated the therapeutic potential of inhibiting c-Abl using imatinib. We developed a novel method, based on a technique used to detect prions (PMCA), to measure minute amounts of misfolded-Aß in the blood of AD transgenic mice. We found that imatinib reduces Aß-oligomers in plasma, which correlates with a reduction of AD brain features such as plaques and oligomers accumulation, neuroinflammation, and cognitive deficits. Cells exposed to imatinib and c-Abl KO mice display decreased levels of ß-CTF fragments, suggesting that an altered processing of the amyloid-beta protein precursor is the most probable mechanism behind imatinib effects. Our findings support the role of c-Abl in Aß accumulation and AD, and propose AD-PMCA as a new tool to evaluate AD progression and screening for drug candidates.

Neuronal gene repression in Niemann-Pick type C models is mediated by the c-Abl/HDAC2 signaling pathway.

BACKGROUND: Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder characterized by the accumulation of free cholesterol in lysosomes. There are currently no effective FDA-approved treatments for NPC, although in the last years the inhibition of histone deacetylases (HDACs) has emerged as a potential treatment for this disease. However, the molecular mechanisms that deregulate HDAC activity in NPC disease are unknown. Previously our group had shown that the proapoptotic tyrosine kinase c-Abl signaling is activated in NPC neurons. Here, we demonstrate that c-Abl activity increases HDAC2 levels inducing neuronal gene repression of key synaptic genes in NPC models. RESULTS: Our data show that: i) HDAC2 levels and activity are increased in NPC neuronal models and in Npc1(-/-) mice; ii) inhibition of c-Abl or c-Abl deficiency prevents the increase of HDAC2 protein levels and activity in NPC neuronal models; iii) c-Abl inhibition decreases the levels of HDAC2 tyrosine phosphorylation; iv) treatment with methyl-ß-cyclodextrin and vitamin E decreases the activation of the c-Abl/HDAC2 pathway in NPC neurons; v) in vivo treatment with two c-Abl inhibitors prevents the increase of HDAC2 protein levels in the brain of Npc1(-/-) mice; and vi) c-Abl inhibition prevents HDAC2 recruitment to the promoter of neuronal genes, triggering an increase in their expression. CONCLUSION: Our data show the involvement of the c-Abl/HDAC2 signaling pathway in the regulation of neuronal gene expression in NPC neuronal models. Thus, inhibition of c-Abl could be a pharmacological target for preventing the deleterious effects of increased HDAC2 levels in NPC disease.

Circulating biomarkers in advanced renal cell carcinoma: clinical applications.

Advances in understanding the biology of renal cell carcinoma (RCC) have resulted in treatment strategies based on molecularly targeted agents that have substantially improved the outcomes of patients with metastatic RCC. Agents targeting the vascular endothelial growth factor pathway and the mammalian target of rapamycin have shown efficacy in randomized clinical trials and received international approval for treating RCC. Multiple candidate biomarkers of the biologic activity of such targeted therapies as well as markers of treatment response and patients' prognosis are being evaluated to improve drug development and to identify patients who may obtain the greatest benefit from the various treatment options. This review summarizes recent developments in identifying circulating biomarkers of targeted therapies for metastatic RCC, including soluble proteins and circulating cells.

Vasoproliferative tumors of ocular fundus: ultrasonographic characteristics.

The aim of this work is to describe ultrasonographic features in vasoproliferative tumors of ocular fundus (VPTOF). The charts of eight patients were retrospectively studied. Clinical data obtained by complete ophthalmologic examination and ultrasonographic findings were analyzed. Nodular masses affecting either the retina alone or the retina and the choroid were found. The surface contour of the tumor was regular in 5 and irregular in 3 cases. In dimensions, the mean (+/- SD) major base was 7.14 +/- 2.56 mm, minor base 6.74 +/- 2.48 mm, and height 2.38 +/- 1.26 mm. Internal structure was always solid and irregular, while reflectivity was mostly medium, and high in 6 eyes. Kappa angle was not present in any case. No signs of vascularity were detected. According to the results, it is suggested that ultrasonographic examination be performed along with ophthalmoscopy on differential diagnosis of VPTOF.

Ultrasonographic findings in circumscribed choroidal hemangioma after photodynamic therapy.

Circumscribed choroidal hemangioma (CCH) is a benign and relatively rare tumor located posteriorly to the equator. The most frequently associated clinical finding is an exudative retinal detachment (ERD). The aim of this work is to describe ultrasonographic findings in eyes diagnosed with CCH + ERD after photodynamic therapy (PDT). Five eyes of five patients diagnosed with CCH (2 men and 3 women; 3 right eyes and 2 left eyes; mean age 50.6 (range 42-63) years) were referred to the Unit of Ocular Oncology. All cases were selected for PDT since all of them showed a macula-off ERD and hence poor visual acuity. The PDT protocol consisted of verteporfin 6 mg/m2 body surface area and exposure to laser light dose at 689 nm at an intensity of 600 mW/cm2 (1 to 3 sessions depending on the persistence of ERD). Ultrasonographic examination was performed by use of the I3-ABD System (posterior segment 10 MHz B-scan and 8 MHz standardized diagnostic A-scan probes, Innovative Imaging Inc., Sacramento, CA, USA). Ultrasonographic findings recorded on the first examination were consistent with those previously described for CCH in the literature. Dimensions of the tumors were very similar in all cases. However, after PDT we detected significant reduction of the height of the tumor and increased reflectivity, without changes in internal structure. Moreover, we detected retinal reattachment in all cases and therefore a slight improvement in visual acuity. Significant changes in ultrasonographic findings can be found after PDT for CCH.

[Meningeal and Guillain-Barrè syndrome in a patient with rheumatoid arthritis receiving adalimumab therapy]. / Síndrome meníngeo y síndrome de Guillain-Barrè en un paciente con artritis reumatoide tratado con adalimumab.

Adalimumab is a recombinant human monoclonal antibody that blocks the effects of tumor necrosis factor-alpha, and is presently used for treatment of rheumatoid arthritis, with demyelination being a potential adverse effect. A 31 year-old male with seropositive rheumatoid arthritis presented with diarrhea after the second injection of adalimumab. He was treated with ciprofloxacin. In a few days he developed a Guillain-Barrè syndrome confirmed by electromyography, and his cerebrospinal fluid was compatible with meningeal syndrome or partially treated bacterial meningitis. Adalimumab may be associated with the development of demyelination and infectious diseases. Moreover, both the central nervous system and the peripheral nervous system can be affected.

Insulin regulates GLUT1-mediated glucose transport in MG-63 human osteosarcoma cells.

Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. Because cancer cells utilize glucose as their primary energy substrate, the expression and regulation of glucose transporters (GLUT) may be important in tumor development and progression. GLUT expression has not been studied previously in human osteosarcoma cell lines. Furthermore, although insulin and insulin-like growth factor (IGF-I) play an important role in cell proliferation and tumor progression, the role of these hormones on GLUT expression and glucose uptake, and their possible relation to osteosarcoma, have also not been studied. We determined the effect of insulin and IGF-I on GLUT expression and glucose transport in three well-characterized human osteosarcoma cell lines (MG-63, SaOs-2, and U2-Os) using immunocytochemical, RT-PCR and functional kinetic analyses. Furthermore we also studied GLUT isoform expression in osteosarcoma primary tumors and metastases by in situ hybridization and immunohistochemical analyses. RT-PCR and immunostaining show that GLUT1 is the main isoform expressed in the cell lines and tissues studied, respectively. Immunocytochemical analysis shows that although insulin does not affect levels of GLUT1 expression it does induce a translocation of the transporter to the plasma membrane. This translocation is associated with increased transport of glucose into the cell. GLUT1 is the main glucose transporter expressed in osteosarcoma, furthermore, this transporter is regulated by insulin in human MG-63 cells. One possible mechanism through which insulin is involved in cancer progression is by increasing the amount of glucose available to the cancer cell.