Differential effects of acute cardiovascular exercise on explicit and implicit motor memory: The moderating effects of fitness level.

A single bout of cardiovascular exercise (CE) performed after practice can facilitate the consolidation of motor memory. However, the effect is variable and may be modulated by different factors such as the motor task's or participant's characteristics and level of awareness during encoding (implicit vs explicit learning). This study examines the effects of acute CE on the consolidation of motor sequences learned explicitly and implicitly, exploring the potential moderating effect of fitness level and awareness. Fifty-six healthy adults (24.1 ± 3.3 years, 32 female) were recruited. After practicing with either the implicit or explicit variant of the Serial Reaction Time Task (SRTT), participants either performed a bout of 16 min of vigorous CE or rested for the same amount of time. Consolidation was quantified as the change in SRTT performance from the end of practice to a 24 h retention test. Fitness level (V̇O2peak) was determined through a graded exercise test. Awareness (implicit vs explicit learning) was operationalized using a free recall test conducted immediately after retention. Our primary analysis indicated that CE had no statistically significant effects on consolidation, regardless of the SRTT's variant utilized during practice. However, an exploratory analysis, classifying participants based on the level of awareness gained during motor practice, showed that CE negatively influenced consolidation in unfit participants who explicitly acquired the motor sequence. Our findings indicate that fitness level and awareness in sequence acquisition can modulate the interaction between CE and motor memory consolidation. These factors should be taken into account when assessing the effects of CE on motor memory.

Detección selectiva del ganglio centinela tras administración intratumoral del radiotrazador, en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante en relación con el grado de respuesta tumoral / Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumour response

Objetivo. Nuestro objetivo fue analizar el rendimiento de la biopsia selectiva del ganglio centinela valorando la detección gammagráfica tras la administración intratumoral del radiofármaco en pacientes con cáncer de mama que recibieron quimioterapia neoadyuvante. Material y métodos. Sesenta pacientes con diagnóstico de carcinoma infiltrante de mama, estadios T1-T3, que recibieron tratamiento con quimioterapia neoadyuvante fueron sometidas posteriormente a cirugía mamaria y biopsia del ganglio centinela mediante administración intratumoral del radiofármaco. Resultados. Se consiguió la detección gammagráfica de algún ganglio centinela en 55/60 pacientes (91,6%). Cuando se excluyeron los casos con reinyección periareolar del radiofármaco por falta de migración, la detección fue del 70% (42/60). Cuando se comparó la detección o no del ganglio centinela en estas 42 pacientes, no se encontraron diferencias en función de la edad, lateralidad-localización de la lesión, tamaño pre y posquimioterapia, grado histológico del tumor o perfil inmunohistoquímico. Sí existieron diferencias significativas al comparar los grupos según el grado de respuesta patológica del tumor, valorado tanto con el sistema de Miller-Payne (no detección 44,4%-detección 16,7%, p = 0,003) como con el sistema residual cancer burden (72,2%-28,6%, p<0,01). Conclusiones. La detección gammagráfica del ganglio centinela tras administración intratumoral del radiofármaco en pacientes con cáncer de mama que recibieron quimioterapia neoadyuvante estuvo por debajo del valor óptimo, siendo necesaria en ocasiones la reinyección periareolar, lo que podría estar en relación con una alteración de las vías de drenaje linfático. Existió una significativa relación inversa entre detección del ganglio centinela y el grado de respuesta patológica tumoral (AU)

Purpose. Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. Materials and methods. The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. Results. Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, p<0.01). Conclusions. The scintigraphic detection of the sentinel node after intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response (AU)

Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumour response. / Detección selectiva del ganglio centinela tras administración intratumoral del radiotrazador, en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante en relación con el grado de respuesta tumoral.

PURPOSE: Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. MATERIALS AND METHODS: The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. RESULTS: Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, p<0.01). CONCLUSIONS: The scintigraphic detection of the sentinel node after intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response.

Novel Water-Soluble Mucoadhesive Carbosilane Dendrimers for Ocular Administration.

The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study. In vitro and in vivo tolerance studies were performed in human ocular epithelial cell lines and rabbit eyes respectively. The interaction of dendrimers with transmembrane ocular mucins was evaluated with a surface biosensor. As proof of concept, the hypotensive effect of a carbosilane dendrimer eyedrop formulation containing acetazolamide (ACZ), a poorly water-soluble drug with limited ocular penetration, was tested after instillation in normotensive rabbits. The methodology used to synthesize cationic dendrimers avoids the difficulty of obtaining neutral -NH2 dendrimers that require harsher reaction conditions and also present high aggregation tendency. Tolerance studies demonstrated that both prototypes of water-soluble anionic and cationic carbosilane dendrimers were well tolerated in a range of concentrations between 5 and 10 µM. Permanent interactions between cationic carbosilane dendrimers and ocular mucins were observed using biosensor assays, predominantly for the generation-three (G3) dendrimer. An eyedrop formulation containing G3 cationic carbosilane dendrimers (5 µM) and ACZ (0.07%) (289.4 mOsm; 5.6 pH; 41.7 mN/m) induced a rapid (onset time 1 h) and extended (up to 7 h) hypotensive effect, and led to a significant increment in the efficacy determined by AUC0(8h) and maximal intraocular pressure reduction. This work takes advantage of the high-affinity interaction between cationic carbosilane dendrimers and ocular transmembrane mucins, as well as the tensioactive behavior observed for these polymers. Our results indicate that low amounts of cationic carbosilane dendrimers are well tolerated and able to improve the hypotensive effect of an acetazolamide solution. Our results suggest that carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.

Mastocitosis cutánea difusa. Presentación de 3 casos y revisión de su manejo terapéutico / Diffuse cutaneous mastocytosis. Presentation of 3 cases and therapeutic management review

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Subcutaneous trastuzumab: drug development and current position

HER2-positive breast cancer, accounting for 15 % of the total breast cancer patient population, carries in itself a bad prognosis, which has now become much better after the advent of anti-HER2 drugs. HER2-targeted therapy has significantly improved disease free- and overall survival in HER2-positive breast cancer, and has rendered better disease control both in the early and advanced disease setting. Trastuzumab treatment duration is often prolonged and poses significant time and resource challenges both on the treatment institutions and on the patient. The recent development of a subcutaneous formulation has meant a significant advance in this respect. We review the drug development of the compound and the current evidence on its use (AU)

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Subcutaneous trastuzumab: drug development and current position.

HER2-positive breast cancer, accounting for 15 % of the total breast cancer patient population, carries in itself a bad prognosis, which has now become much better after the advent of anti-HER2 drugs. HER2-targeted therapy has significantly improved disease free- and overall survival in HER2-positive breast cancer, and has rendered better disease control both in the early and advanced disease setting. Trastuzumab treatment duration is often prolonged and poses significant time and resource challenges both on the treatment institutions and on the patient. The recent development of a subcutaneous formulation has meant a significant advance in this respect. We review the drug development of the compound and the current evidence on its use.

Critical role of the death receptor pathway in the antitumoral effects induced by hispanolone derivatives.

Labdane diterpenoids have a broad spectrum of biological activities including antibacterial, antiviral and anti-inflammatory properties. However, little is known about their possible role in the apoptotic cell death machinery. Here, we report that hispanolone derivatives, a group of labdane diterpenoids, induce apoptosis in different tumor cell lines by activating caspase-8 with subsequent participation of mitochondrial signaling. Activation of caspase-8 by hispanolone derivatives was followed by a decrease in mitochondrial membrane potential, the release of apoptotic factors from mitochondria to the cytosol, and activation of caspases-9 and 3. Hispanolone derivatives also led to a time-dependent cleavage of Bid. Inhibition of caspase-8 abrogated these processes, suggesting that the death receptor pathway has a critical role in the apoptotic events induced by hispanolone derivatives. In addition, silencing death receptors with small interfering RNA s or pretreating cells with neutralizing antibodies to Fas ligand, tumor necrosis factor receptor 1 (TNF-R1), and TNF-α receptor 2 (TRAIL) inhibited diterpenoid-induced apoptosis, revealing it to be dependent on these death receptors. Interestingly, hispanolone derivatives had no effect on non-tumor cells. Consistently, in vivo bioluminescence imaging corroborates this antineoplasic effect, as hispanolone derivatives significantly decrease cancer growth in tumor xenograft assays. These data demostrate the antitumoral effects of hispanolone derivatives and provide relevant preclinical validation for the use of these compounds as potent therapeutic agents in cancer treatment.

Taller de educación para la salud sobre prevención de osteoporosis en mujeres. Efectividad de una intervenciónenfermera en atención primaria / Workshop on health education on prevention of osteoporosis in women. Effectiveness of an intervention in primary care nurse

Los autocuidados son fundamentales para cualquier persona, sana o enferma, tanto en el tratamiento como en la prevención de enfermedades. Un aumento del nivel de autocuidados es deseable en enfermedades crónicas y de elevada prevalencia como la osteoporosis. El objetivo fue proporcionar conocimientos y promover estilos de vida saludables orientados a mejorar la calidad de vida y el autocuidado en mujeres que reciben educación sanitaria sobre la osteoporosis. El diseño del estudio es de intervención comunitaria, abierto, de un solo centro, prospectivo y de 8 meses de duración, desarrollado en el Centro de Salud de Morarzarzal. La muestra fue de 140 mujeres de edades comprendidas entre 40 y 70 años. Todas las participantes rellenaron un test inicial para evaluar su nivel de conocimientos sobre la osteoporosis y estilos de vida. Efectuamos la valoración de enfermería por patrones funcionales de Salud de Marjory Gordon e identificamos, entre otros, problemas relacionados con el manejo adecuado del régimen terapéutico, su conocimiento y ejecución, estableciendo un diagnóstico enfermero. Con el apoyo de la taxonomía NANDA, la NOC y NIC determinamos los objetivos e intervenciones de enfermería. Las mujeres recibieron 4 sesiones de educación sanitaria grupal sobre menopausia y osteoporosis, dieta equilibrada y adecuada orientada hacia la prevención de la enfermedad, ejercicio físico recomendado, corrección postural y manejo de cargas, hábitos tóxicos y de estilos de vida que afectan a la salud ósea. Tras la intervención educativa, las mujeres volvieron a hacer el test de conocimientos y de estilos de vida. A los 8 meses de finalizar los talleres educativos valoramos los resultados el Plan de Cuidados. El estudio estadístico consistió en comparar los valores de las variables seleccionadas antes y después de la intervención educativa. Las variables cuantitativas se analizaron con test paramétricos (t de Student para datos apareados) y con no paramétricos (test U de Mann Whitney). La potencia escogida para los test fue del 80% y el nivel de significación p<0,05. Al estudiar las diferencias entre los resultados se pretendía averiguar si la intervención educativa grupal y el posterior seguimiento del plan de cuidados en consulta de enfermería fueron efectivos para mejorar los autocuidados y la calidad de vida de las mujeres participantes en el estudio. Obtuvimos los resultados esperados del Plan de Cuidados (AU)

The increase of self-care is crucial for any person, healthy or ill, during his treatment or for preventing any illness. This is applicable to osteoporosis, a chronic illness with a high prevalence. Objective: To increase knowledge and promote healthy life styles to improve live quality and self-care for women receiving health education on osteoporosis. Design: Open community intervention trial, prospective during 8 months, developed in a single center: Moralzarzal Health Center. The sample included 140 women aged between 40 and 70. All participants completed an initial test to assess their level of knowledge about osteoporosis and lifestyles. We performed nursing assessment by Marjory Gordon’s Health functional patterns and we identified, among others, problems related to proper management of therapeutic regimen, its knowledge and its execution, establishing a nursing diagnosis. We determined the goals and nursing interventions with the support of taxonomy NANDA, NOC and NIC. The women received four sessions of group health education about menopause and osteoporosis, balanced and adequate diet oriented to disease prevention, recommended physical activity, postural correction and load management, bad habits and lifestyles that affect bone health. After the educational intervention, the women completed again the test of knowledge and lifestyles, and 8 months after the educational workshops’ end, we valued the Care Plan results. The statistical study was to compare the values of selected variables before and after the educational intervention. Quantitative variables were analyzed using parametric tests (Student t test for paired data) or nonparametric (Mann Whitney U test). The power chosen for the test was 80% and significance level p <0.05. By studying the differences in results we wanted to determine if the educational intervention and subsequent monitoring of the care plan in nursing consultations were effective in improving self-care and quality of life of women participating in the study. We obtained the expected results of the Plan of Care (AU)

Labdane diterpenes protect against anoxia/reperfusion injury in cardiomyocytes: involvement of AKT activation.

Several labdane diterpenes exert anti-inflammatory and cytoprotective actions; therefore, we have investigated whether these molecules protect cardiomyocytes in an anoxia/reperfusion (A/R) model, establishing the molecular mechanisms involved in the process. The cardioprotective activity of three diterpenes (T1, T2 and T3) was studied in the H9c2 cell line and in isolated rat cardiomyocyte subjected to A/R injury. In both cases, treatment with diterpenes T1 and T2 protected from A/R-induced apoptosis, as deduced by a decrease in the percentage of apoptotic and caspase-3 active positive cells, a decrease in the Bcl-2/Bax ratio and an increase in the expression of antiapoptotic proteins. Analysis of cell survival signaling pathways showed that diterpenes T1 and T2 added after A/R increased phospho-AKT and phospho-ERK 1/2 levels. These cardioprotective effects were lost when AKT activity was pharmacologically inhibited. Moreover, the labdane-induced cardioprotection involves activation of AMPK, suggesting a role for energy homeostasis in their mechanism of action. Labdane diterpenes (T1 and T2) also exerted cardioprotective effects against A/R-induced injury in isolated cardiomyocytes and the mechanisms involved activation of specific survival signals (PI3K/AKT pathways, ERK1/2 and AMPK) and inhibition of apoptosis.

Anti-inflammatory and antioxidant properties of a new arylidene-thiazolidinedione in macrophages.

Thiazolidinediones (TZDs) are a class of drugs used for treatment of type 2 diabetes. However, the therapy with currently available TDZs (e.g. rosiglitazone) is associated with important side effects, such as edema and weight gain, suggesting that the investigation of alternative TZDs with better pharmacological properties is warranted. In this study, we investigated both anti-inflammatory and antioxidant properties of a new chemically modified TZD, the arylidene-thiazolidinedione 5-(4-methanesulfonyl-benzylidene)-3-(4-nitrobenzyl)-thiazolidine-2,4-dione (SF23), and compared the results to those obtained with rosiglitazone. We found that our SF23 displays a weaker affinity for PPARγ, up-regulating in a lower magnitude the expression of both PPARγ and CD36 compared to rosiglitazone. In lipopolysaccharide (LPS)-stimulated macrophages, SF23 decreased nitrite production and attenuated the mRNA expression of both iNOS and COX-2. These anti-inflammatory effects were comparable to those obtained with rosiglitazone. Interestingly, SF23, but not rosiglitazone, prevented LPS-induced mitochondrial membrane hyperpolarization, apoptosis, reactive oxygen species (ROS) generation, and the expression of NADPH oxidase subunits, Nox1 and Nox2. In addition, in macrophages from Nrf2⁻/⁻ mice, SF23 protected against LPSinduced cellular death and ROS production, whereas rosiglitazone was only able to protect normal Nrf2⁺/⁺ cells against oxidative injury, suggesting that, unlike rosiglitazone, the antioxidant activity of SF23 might be Nrf2-independent. Finally, in macrophages exposed to high concentrations of glucose, SF23 induced significant increases in the mRNA expression of glucose transporters, insulin receptor substrate and mitoNEET. Altogether, our data indicate that our new chemically modified TDZ displays similar anti-inflammatory properties, but superior antioxidant effects on the LPS-stimulated macrophages compared to rosiglitazone.

Expression and crystallization of SeDsbA, SeDsbL and SeSrgA from Salmonella enterica serovar Typhimurium.

Pathogens require protein-folding enzymes to produce functional virulence determinants. These foldases include the Dsb family of proteins, which catalyze oxidative folding in bacteria. Bacterial disulfide catalytic processes have been well characterized in Escherichia coli K-12 and these mechanisms have been extrapolated to other organisms. However, recent research indicates that the K-12 complement of Dsb proteins is not common to all bacteria. Importantly, many pathogenic bacteria have an extended arsenal of Dsb catalysts that is linked to their virulence. To help to elucidate the process of oxidative folding in pathogens containing a wide repertoire of Dsb proteins, Salmonella enterica serovar Typhimurium has been focused on. This Gram-negative bacterium contains three DsbA proteins: SeDsbA, SeDsbL and SeSrgA. Here, the expression, purification, crystallization and preliminary diffraction analysis of these three proteins are reported. SeDsbA, SeDsbL and SeSrgA crystals diffracted to resolution limits of 1.55, 1.57 and 2.6 A and belonged to space groups P2(1), P2(1)2(1)2 and C2, respectively.

The effect of preservative-free HP-Guar on dry eye after phacoemulsification: a flow cytometric study.

PURPOSE: To assess the effect of hydroxypropyl (HP)-Guar added to regular post-phacoemulsification treatment in dry eye signs and symptoms, and its influence on the expression of various inflammatory markers by flow cytometry (FCM) in impression cytology specimens. METHODS: This prospective, interventional, single-centre study included 48 eyes of 48 patients with age-related cataract. After phacoemulsification, patients were randomised to the usual treatment group (UT), with 21 patients who received tobramycin and dexamethasone eye drops (Tobradex, Alcon Cusí, Spain), and the HP-Guar group, with 27 patients who received the UT plus preservative-free artificial tears (Systane UD, Alcon Cusí, Spain). Corneal and conjunctival staining with fluorescein and lissamine green, tear film break-up time (TBUT), Schirmer's I test with anaesthesia (Jones test), tear clearance, and ocular surface disease index (OSDI) were assessed preoperatively and 1 month after surgery. Besides, conjunctival impression cytology was performed in order to investigate inflammatory markers (CD3, CD11b, and HLA-DR) using FCM. RESULTS: HP-Guar group shows statistical better results compared with the UT group in TBUT (6.4+/-0.7 vs 9+/-2.5, P=0.0004), OSDI (11.5+/-8.2 vs 3.3+/-2.5, P=0.0002), ocular symptoms subscale (7.3+/-6.1 vs 1.7+/-1.8, P=0.0004), vision-related function subscale (2.2+/-1.8 vs 0.4+/-0.6, P=0.0002), CD3 (2.5+/-1.4 vs 1.1+/-1.1, P=0.011), and HLA-DR (6.8+/-4.5 vs 1.8+/-1.7, P=0.0002). CONCLUSION: The addition of HP-Guar to regular treatment after cataract surgery reduces ocular surface inflammation and dry eye signs and symptoms.

Resultados clínicos y laborales de las fracturas de la extremidad proximal del humero tratada con placas PHILOS® / Clinical-laboral results of proximal humerus fracture treated with PHILOS® plates fixation

Objetivo: Valorar el resultado clínico y laboral de la osteosíntesis con placa PHILOS® en las fracturas de la extremidad proximal del húmero. Pacientes y método: Estudio retrospectivo de 16 pacientes con fractura desplazada de la extremidad proximal del húmero intervenidos con osteosíntesis mediante placa PHILOS®. La edad media fue de 42 (rango: 16-59) años, el 62% eran varones, el hombro dominante se afectó en el 38% de los casos. Estudiamos el tipo de fractura según la clasificación de Neer, valoración clínica, valoración funcional y resultados laborales. Resultados: El tiempo medio hasta la cirugía fue de 13 dias, el tiempo medio de rehabilitación de 6 meses y medio y el tiempo medio de baja de 7 meses. La puntuación en el test de Constant fue 73.3 (27-100), siendo peor en los pacientes con fractura luxación. Se incorporaron a su trabajo habitual 10 de los 16 pacientes. Conclusión: La osteosíntesis con placa PHILOS es un método eficaz en el tratamiento de las fracturas de la extremidad proximal del húmero, con buenos resultados tanto clínicos, como laborales. Nivel de evidencia: Estudio terapéutico, serie de casos, Nivel IV (AU)

Aim: The assessment of PHILOS plate fixation for displaced proximal humeral fractures clinical and laboral outcomes. Patients and method: A retrospective study, 16 patients with fractures of the proximal humerus underwent to Philos plate fixation from January 2007 to December 2008 at the Hospital Majadahonda Fremap. Type of fracture according to Neer classification, clinical assessment, functional assessment and laboral result were studied. esults: The average age was 42 (range: 16-59), 62% were males, and the dominant shoulder was affected in 38% of cases. The mean time to surgery was 13 days, the average rehabilitation time of 6.5 months and mean time on sick leave is of 7.5 months. Three patients required additional treatments (mobilization under anesthesia, removal of osteosynthesis material and one patient required both procedures) only. Constant test score was 73.3 (range: 27- 100), being worse in patients with fracture dislocation. 10 of the 16 patients returned to their usual work. Concluding remarks: The Plate Philos is an effective method in the treatment of fractures of the proximal humerus, showing good results both regarding clinical and occupational outcomes. Level of Evidence: Therapeutic study, level IV (case series) (AU)

Electronegative LDL induction of apoptosis in macrophages: involvement of Nrf2.

The aim of this study was to determine the apoptotic pathways and mechanisms involved in electronegative LDL [LDL(-)]-induced apoptosis in RAW 264.7 macrophages and the role of Nrf2 in this process. Incubation of RAW 264.7 macrophages with LDL(-) for 24 h resulted in dose-dependent cell death. Activated caspases were shown to be involved in the apoptosis induced by LDL(-); incubation with the broad caspase inhibitor z-VAD prevented apoptosis in LDL(-)-treated cells. CD95 (Fas), CD95 ligand (FasL), CD36 and the tumor necrosis factor (TNF) ligand Tnfsf10 were overexpressed in LDL(-)-treated cells. However, Bax, Bcl-2 and Mcl-1 protein levels remained unchanged after LDL(-) treatment. LDL(-) promoted hyperpolarization of the mitochondrial membrane, elevated reactive oxygen species (ROS) production and translocation of Nrf2 to the nucleus, a process absent in cells treated with native LDL. Elicited peritoneal macrophages from Nrf2-deficient mice exhibited an elevated apoptotic response after challenge with LDL(-), together with an increase in the production of ROS in the absence of alterations in CD36 expression. These results provide evidence that CD36 expression induced by LDL(-) is Nrf2-dependent. Also, it was demonstrated that Nrf2 acts as a compensatory mechanism of LDL(-)-induced apoptosis in macrophages.

Molecular basis of the anti-inflammatory effects of terpenoids.

Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Among them, terpenoids (also referred to as terpenes), are the largest and most widespread class of secondary metabolites. They are found in higher plants, mosses, liverworts, algae and lichens, and also in insects, microbes or marine organisms. Some terpenoids have been used for therapeutic purposes for centuries as antibacterial, anti-inflammatory, antitumoral agents, and in recent decades research activity into the clinical potential of this class of compounds has increased continuously as a source of pharmacologically interesting agents. In the present review, molecular basis of the anti-inflammatory action of diterpenoids is presented with special emphasis on their ability to modulate critical cell signaling pathways involved in the inflammatory response of the body such as nuclear transcription factor-kappaB (NF-kappaB) activation. NF-kappaB plays an important role in the regulation of immune and inflammatory responses. Indeed, deregulated NF-kappaB expression is a characteristic phenomenon in several inflammatory diseases and NF-kappaB has become a major target in drug discovery. Hence, this article also introduces our recently elucidated findings about the potential of labdane diterpenoids as anti-inflammatory agents due to their ability to inhibit NF-kappaB. The future development of this class of compounds as anti-inflammatory drugs requires the introduction of novel molecular targets of therapeutic relevance in addition to biotechnological approaches for the production of these molecules.

Análisis descriptivo de los trastornos y problemas psicológicos en pacientes con cáncer de mama / No disponible

Objetivos: Analizar la proporción de pacientes con cáncerde cáncer de mama derivadas a la Unidad de Psico-Oncologíaprocedentes de la Unidad de Patología Mamaria del Serviciode Hematología y Oncología Médica del Hospital Clínico Universitariode Valencia durante el periodo 2005-2007, asícomo el diagnóstico psicológico de estas pacientes.Método: Las pacientes fueron derivadas por su especialista,mediante hoja de interconsulta. La recogida de datos fuediaria mediante hoja de trabajo creada para tal fin, incorporandoesta información a la base de datos del hospital.Resultados: A la Unidad de Psico-Oncología se derivaron189 pacientes procedentes de la Unidad de Patología Mamaria,lo que representa el 15,25% de pacientes; sin embargopara Unidad de Psico-Oncología representa el 42% de todoslos pacientes atendidos en primera visita durante el periodo.Su media de edad, fue de 51,58 años (rango 30-77). Se realizaron772 visitas sucesivas a estas pacientes, lo que representael 59% de todas las visitas sucesivas realizadas, la media devisitas fue de 4 por paciente.En cuanto a los diagnósticos psicológicos, el 50% presentódiagnóstico DSM-IV. Los diagnósticos psicológicos más frecuentesfueron los trastornos adaptativos con un 53% del total.Conclusiones: Un tercio de pacientes con cáncer de mamafueron derivadas a la Unidad de Psico-Oncología, siendo estaproporción menor a los datos referidos en la bibliografía.Respecto a los diagnósticos psicológicos la mitad de estas pacientespresentaron diagnóstico DSM-IV siendo los más frecuenteslos trastornos adaptativos, posiblemente, esta alta prevalenciade patología puede deberse a la selección realizada.En cuanto a la Unidad de Psico-Oncología, la atención apacientes con cáncer de mama representó más de la mitad denuestra actividad asistencial...(AU)

Objectives: To analyze the proportion of breast cancer patientsreferred to the Psychooncology Unit from the BreastPathology Unit, Department of Hematology and Oncology,University Clinic Hospital, Valencia during the period 2005 –2007, as well as the psychological diagnosis of these patients.Methods: Patients were referred by their consultant. Datawere collected daily on a specifically-designed form, incorporatingthis information into the hospital data base.Results: One hundred eighty-nine patients were referredfrom the Breast Pathology Unit (representing 15.25% of theirpatients) to the Psychooncology Unit (corresponding to 42%of all patients seen at this Unit as a first visit during the sameperiod). The mean age was 51.58 years (range 30-77). Thepatients received 772 successive visits, representing 59% of allsuccessive visits made, with a mean of 4 visits per patient.Regarding psychological diagnosis, 50% presented DSMIV.The most frequent diagnosis was adjustment disorder,comprising 53% of the total.Conclusions: One third of breast cancer patients were referredto the Psychooncology Unit; this proportion is lower thanthat found in the literature.Regarding psychological diagnosis, half these patients presentedDSM-IV, the most frequent diagnosis was adjustmentdisorder, this high prevalence possibly being due to the sampleselected.For the Psychooncology Unit, care for breast cancer patientsrepresents half of our welfare activities. We believe it isessential to establish referral criteria that favor the detection ofemotional problems amenable to psychooncologic intervention(AU)

Crystallization and preliminary diffraction analysis of a DsbA homologue from Wolbachia pipientis.

alpha-DsbA1 is one of two DsbA homologues encoded by the Gram-negative alpha-proteobacterium Wolbachia pipientis, an endosymbiont that can behave as a reproductive parasite in insects and as a mutualist in medically important filarial nematodes. The alpha-DsbA1 protein is thought to be important for the folding and secretion of Wolbachia proteins involved in the induction of reproductive distortions. Crystals of native and SeMet alpha-DsbA1 were grown by vapour diffusion and belong to the monoclinic space group C2, with unit-cell parameters a = 71.4, b = 49.5, c = 69.3 A, beta = 107.0 degrees and one molecule in the asymmetric unit (44% solvent content). X-ray data were recorded from native crystals to a resolution of 2.01 A using a copper anode and data from SeMet alpha-DsbA1 crystals were recorded to 2.45 A resolution using a chromium anode.

Valoración clínica y radiográfica de la meniscectomía y reparación de la rotura del ligamento cruzado anterior con 10 años de evolución / Clinical and radiographic assessment of meniscectomy and repair of the anterior cruciate ligament rupture ten years after surgery

Objetivo: valorar la situación funcional y radiográfica de los pacientes que fueron intervenidos de meniscectomía, ligamentoplastia de LCA o ambas 10 años después de las cirugías. Material y Método: revisamos 35 pacientes intervenidos de meniscectomía parcial, ligamentoplastia con tendones de la pata de ganso por rotura del LCA, o ambas técnicas conjuntas, en 1997. Evaluamos el índice de satisfacción (escala 1-10), cuestionario KOOS (Knee Osteoarthritis Outcome Score) y el grado de gonartrosis en radiografía antero- posterior y lateral en carga, siguiendo la escala de Kellgren-Lawrence. Se efectuó un análisis de los datos obtenidos en cada grupo para efectuar un estudio descriptivo de los mismos. Resultados: la meniscectomía fue un factor de riesgo para el desarrollo de artrosis, no hemos demostrado que la reconstrucción del LCA con tendones de pata de ganso favorezca la gonartrosis a medio plazo, casi el 70% de los pacientes no tenía signos degenerativos y los que los presentaron se encuadraron en un grado I. Tampoco establecimos una relación entre la presencia de signos de artrosis radiográfica y la percepción de calidad de vida. En nuestros casos, ambas cirugías tienen una evolución clínica a medio plazo que permite al paciente una buena calidad de vida y una actividad laboral normal, si bien la ligamentoplastia aislada de LCA obtiene mejores puntuaciones en el cuestionario KOOS con menor incidencia de artrosis en la imagen (AU)

Objective: To assess the functional and radiographic status of patients operated upon for meniscectomy and/or ligamentoplasty of the anterior cruciate ligament (ACL) 10 years after surgery. Material and method: We reviewed 35 patients operated upon in 1997 for partial meniscectomy, ligamentoplasty with goosefoot tendons for rupture of the ACL, or both techniques in combination. We evaluated the satisfaction index (1-10 scale), KOOS questionnaire (Knee Osteoarthritis Outcome Score) and the degree of gonarthrosis in antero-posterior and lateral weight-bearing radiography, following the Kellgren-Lawrence scale. The data obtained from each group were analyzed and subjected to descriptive study. Results: Meniscectomy was a risk factor for the development of osteoarthritis. We have not shown reconstruction of the ACL with goosefoot tendons to enhance gonarthrosis over the middle term; almost 70% of all patients had no degenerative signs, and those who did were rated as grade I. Likewise, no relationship was established between the presence of signs of radiographic osteoarthritis and patient perceived quality of life. In our cases, both surgical interventions offer middle term clinical results affording patients a good quality of life and normal working activity, though ACL ligamentoplasty alone obtains better scores according to the KOOS questionnaire, with a lesser incidence of osteoarthritis as determined by imaging techniques (AU)