Terapia con péptidos radiomarcados con [177Lu]Lu-DOTA-TATE / Peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE

Esta formación pretende presentar, de forma clara y de fácil comprensión, la biología de los tumores neuroendocrinos (TNE), las características de los receptores de somatostatina, cómo debe realizarse la selección de pacientes candidatos a terapia con péptidos radiomarcados (PRRT), si el paciente cumple los criterios para beneficiarse del tratamiento con los mínimos efectos adversos posibles, el protocolo de administración, seguimiento y evaluación de respuesta. También, se desarrollan los estudios de imagen funcional necesarios para explorar la biología del tumor e individualizar el tratamiento, que constituyen la piedra angular para el desarrollo de la teragnosis.Se están desarrollando ensayos clínicos para definir mejor la posición de PRRT dentro del amplio panorama terapéutico y, entre las perspectivas de futuro, hay varias líneas de investigación para mejorar la tasa de respuesta objetiva y la supervivencia con PRRT, centradas en el desarrollo de nuevos agonistas y antagonistas del receptor de somatostatina, nuevos radionúclidos y terapias combinadas radiosensibilizantes.En conclusión, la PRRT es un tratamiento bien tolerado, seguro y con efectos secundarios agudos, generalmente leves y autolimitados, que constituye una gran herramienta terapéutica que debe secuenciarse en el mejor momento de la evolución de la enfermedad de los pacientes con TNE. Los pacientes candidatos a la PRRT deben ser valorados siempre por un comité clínico multidisciplinar (AU)

This continuing education aims to present in a clear and easy-to-understand way, the biology of neuroendocrine tumors (NETs), the characteristics of somatostatin receptors, the selection of patients for radiolabelled peptide therapy (PRRT), the inclusion criteria to benefit from treatment with the minimum possible adverse effects, the administration protocol, follow-up and response evaluation. The functional imaging studies necessary to explore the biology of the tumor and to individualize the treatment are also carried out, and constitute the cornerstone for the development of teragnosis.Clinical trials are being developed to better define the position of PRRT within the broad therapeutic options, and among the future perspectives, there are several lines of research to improve the objective response rate and survival with PRRT, focused on the development of new agonists and somatostatin receptor antagonists, new radionuclides and radiosensitizing combination therapies.In conclusion, PRRT is a great therapeutic, well-tolerated and safe tool with generally mild and self-limited acute side effects, that must be sequenced at the best moment of the evolution of the disease of patients with NET. Candidate patients for PRRT should always be evaluated by an multidisciplinary clinical committee (AU)

Peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE.

This continuing education aims to present in a clear and easy-to-understand way, the biology of neuroendocrine tumors (NETs), the characteristics of somatostatin receptors, the selection of patients for radiolabelled peptide therapy (PRRT), the inclusion criteria to benefit from treatment with the minimum possible adverse effects, the administration protocol, follow-up and response evaluation. The functional imaging studies necessary to explore the biology of the tumor and to individualize the treatment are also carried out, and constitute the cornerstone for the development of teragnosis. Clinical trials are being developed to better define the position of PRRT within the broad therapeutic options, and among the future perspectives, there are several lines of research to improve the objective response rate and survival with PRRT, focused on the development of new agonists and somatostatin receptor antagonists, new radionuclides and radiosensitizing combination therapies. In conclusion, PRRT is a great therapeutic, well-tolerated and safe tool with generally mild and self-limited acute side effects, that must be sequenced at the best moment of the evolution of the disease of patients with NET. Candidate patients for PRRT should always be evaluated by a multidisciplinary clinical committee.

Efectos de la rehabilitación pulmonar sobre los síntomas asociadosa las exacerbaciones en pacientes / Effects of pulmonary rehabilitation on symptoms associated with exacerbations in patients with COPD

Las exacerbaciones de enfermedad pulmonar obstructiva crónica (EPOC) son responsables del deterioro físico de los pacientes, del ingreso y reingreso hospitalario, así como de su muerte. Esta revisión evidencia los beneficios de la rehabilitación pulmonar en la reducción de episodios de exacerbaciones en la EPOC. La metodología de búsqueda abarcó un total de 2.473 artículos, de los cuales fueron usados 14 para esta revisión según el cumplimiento de criterios establecidos. Los resultados obtenidos fueron significativos en las siguientes variables vinculadas directamente con la frecuencia de los episodios de exacerbación: disnea, saturación de oxígeno, volumen espiratorio forzado en el primer segundo, días de hospitalización, número de reingresos hospitalarios, capacidad de ejercicio, depresión y calidad de vida. La rehabilitación pulmonar mostró efectos positivos en las variables mencionadas, disminuyendo los episodios de exacerbaciones de la EPOC como las limitaciones en las actividades de los pacientes (AU)

Exacerbations of chronic obstructive pulmonary disease (COPD) are responsible for the physical deterioration of patients, hospital admission and readmission, as well as their death. This review demonstrates the benefits of pulmonary rehabilitation in reducing exacerbation episodes in COPD. A search was carried obtained a total of 2473 articles, of which 14 were used for this review according to the fulfillment of established criteria. The results obtained were significant in relation to the variables directly related to the frequency of exacerbation episodes: dyspnea, oxygen saturation, forced expiratory volume in the first second, days of hospitalization, number of hospital readmissions, exercise capacity, depression and quality of life. Pulmonary rehabilitation causes positive effects on the aforementioned variables, reducing episodes of COPD exacerbations as well as limitations in patients’ activities (AU)

LPA1 receptor and chronic stress: Effects on behaviour and the genes involved in the hippocampal excitatory/inhibitory balance.

The LPA1 receptor, one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts, is likely involved in promoting normal emotional behaviours. Current data suggest that the LPA-LPA1-receptor pathway may be involved in mediating the negative consequences of stress on hippocampal function. However, to date, there is no available information regarding the mechanisms whereby the LPA1 receptor mediates this adaptation. To gain further insight into how the LPA-LPA1 pathway may prevent the negative consequences of chronic stress, we assessed the effects of the continuous delivery of LPA on depressive-like behaviours induced by a chronic restraint stress protocol. Because a proper excitatory/inhibitory balance seems to be key for controlling the stress response system, the gene expression of molecular markers of excitatory and inhibitory neurotransmission was also determined. In addition, the hippocampal expression of mineralocorticoid receptor genes and glucocorticoid receptor genes and proteins as well as plasma corticosterone levels were determined. Contrary to our expectations, the continuous delivery of LPA in chronically stressed animals potentiated rather than inhibited some (e.g., anhedonia, reduced latency to the first immobility period), though not all, behavioural effects of stress. Furthermore, this treatment led to an alteration in the genes coding for proteins involved in the excitatory/inhibitory balance in the ventral hippocampus and to changes in corticosterone levels. In conclusion, the results of this study reinforce the assumption that LPA is involved in emotional regulation, mainly through the LPA1 receptor, and regulates the effects of stress on hippocampal gene expression and hippocampus-dependent behaviour.

Desarrollo de solución inyectable de ribavirina en el Centro Militar de Farmacia de la Defensa como tratamiento de urgencia frente a agentes víricos altamente infecciosos. Cobertura de una laguna terapéutica / Development of the injectable ribavirin solution at the Military Defense Pharmacy Center as an emergency treatment against highly infectious agents. Coverage of a therapeutic lagoon

Antecedentes: España por su situación geopolítica no está exenta de amenazas y desafíos asociados a enfermedades infecciosas víricas como las «fiebres hemorrágicas víricas». Implementar acciones para disminuir estos riesgos frente a agentes víricos con el desarrollo de un tratamiento de urgencia por vía intravenosa resulta de gran interés. Objetivos: Desarrollar dos formulaciones de Ribavirina 100 mg/ml con distintos excipientes y condiciones de fabricación para buscar la formulación más estable. Material y métodos: Se ha utilizado ribavirina, distintos tampones y agua para inyectables. Se ha evaluado alteraciones físicas, riqueza y pH siguiendo especificaciones de la monografía de la Farmacopea Europea. Resultados: Se exponen resultados de pH y riqueza de ambas formulaciones con y sin esterilización terminal. Conclusiones: Los resultados obtenidos cumplen especificaciones para ambas formulaciones, demostrando una estabilidad química tras su conservación en condiciones de estudios a largo plazo durante 12 meses y acelerados durante 6 meses. El desarrollo de la ribavirina 100 mg/ml (10% w/v) inyectable satisface una necesidad terapéutica relacionada con el tratamiento de primera elección en enfermedades víricas altamente contagiosas que carecen de tratamientos eficaces

Background: Spain, due to its geopolitical situation, is not exempt from the threats and challenges associated with viral infectious diseases such as the «viral hemorrhagic fevers». Implementing actions to reduce these risks with the development of an emergency treatment against these viral agents for intravenous is of great interest. Objective: Develop two formulations of Ribavirin 100 mg/ml with different excipients and manufacturing conditions to look for the most stable formulation. Material and methods: Ribavirin, various buffers and water for injections have been used. Physical alterations, richness and pH have been evaluated following specifications of European Pharmacopoeia monograp. Results: Results of pH and richness of both formulations are exposed with and without terminal sterilization. Conclusions: The results obtained meet specifications for both formulations, demonstrating chemical stability after preservation under long-term study conditions for 12 months and accelerated for 6 months. The development of injectable 100 mg/ml ribavirin (10% w/v) satisfies a therapeutic need related to the treatment of first choice in highly contagious viral diseases that lack treatments

Lengua geográfica: ¿qué es lo que un dermatólogo debería saber? / Geographic Tongue: What a Dermatologist Should Know

La lengua geográfica, también conocida como glositis migratoria benigna, es una condición inflamatoria crónica benigna de la lengua. Se caracteriza por presentar lesiones eritematosas asociadas a una atrofia de papilas, las que están rodeadas por áreas blanquecinas bien delimitadas y localizadas predominantemente en la cara lateral y dorsal de la lengua, lo que da una imagen que recuerda un mapa geográfico. Estas lesiones pueden variar tanto de tamaño como de forma durante su evolución; además, presentan periodos de exacerbación y remisión sin dejar lesiones cicatriciales residuales. La causa de esta entidad sigue siendo desconocida, sin embargo, múltiples asociaciones se han descrito, las que son comentadas a continuación

Geographic tongue, also known as benign migratory glossitis, is a benign chronic inflammatory condition of the tongue. It is characterized by erythematous lesions with filiform papillae atrophy, surrounded by white limited areas in the dorsal and lateral aspects of the tongue, producing a map-like aspect. This lesions change in size and shape with time, and are characterized by periods of exacerbation and remission without scaring. The cause is unknown, but multiple associations have been described, which will be discussed below

Geographic Tongue: What a Dermatologist Should Know. / Lengua geográfica: ¿qué es lo que un dermatólogo debería saber?

Geographic tongue, also known as benign migratory glossitis, is a benign chronic inflammatory condition of the tongue. It is characterized by erythematous lesions with filiform papillae atrophy, surrounded by white limited areas in the dorsal and lateral aspects of the tongue, producing a map-like aspect. This lesions change in size and shape with time, and are characterized by periods of exacerbation and remission without scaring. The cause is unknown, but multiple associations have been described, which will be discussed below.

Comparative analysis and characterization of soluble factors and exosomes from cultured adipose tissue and bone marrow mesenchymal stem cells in canine species.

The two main sources of mesenchymal stem cell (MSCs) in the canine species are bone marrow (cBM-MSCs) and adipose tissue (cAd-MSCs). The secretion of multitude bioactive molecules, included under the concept of secretome and found in the cultured medium, play a predominant role in the mechanism of action of these cells on tissue regeneration. Although certain features of its characterization are well documented, their secretory profiles remain unknown. We described and compared, for the first time, the secretory profile and exosomes characterization in standard monolayer culture of MSCs from both sources of the same donor as well as its immunomodulatory potential. We found that despite the similarity in surface immunophenotyping and trilineage differentiation, there are several differences in terms of proliferation rate and secretory profile. cAd-MSCs have advantages in proliferative capacity, whereas cBM-MSCs showed a significantly higher secretory production of some soluble factors (IL-10, IL-2, IL-6, IL-8, IL-12p40, IFN-γ, VEGF-A, NGF-ß, TGF-ß, NO and PGE2) and exosomes under the same standard culture conditions. Proteomics analysis confirm that cBM-MSCs exosomes have a greater number of characterized proteins involved in metabolic processes and in the regulation of biological processes compared to cAd-MSCs. On the other hand, secretome from both sources demonstrate similar immunomodulatory capacity when tested in mitogen stimulated lymphocyte reaction, but not in their exosomes at the dose used. Considering that the use of secretome open as a new therapeutic strategy for different diseases, without the need to implant cells, those biological differences should be considered, when choosing the MSCs source, for either cellular implantation or direct use of secretome for a specific clinical application.

Brain Glucose-Sensing Mechanism and Energy Homeostasis.

The metabolic and energy state of the organism depends largely on the availability of substrates, such as glucose for ATP production, necessary for maintaining physiological functions. Deregulation in glucose levels leads to the appearance of pathological signs that result in failures in the cardiovascular system and various diseases, such as diabetes, obesity, nephropathy, and neuropathy. Particularly, the brain relies on glucose as fuel for the normal development of neuronal activity. Regions adjacent to the cerebral ventricles, such as the hypothalamus and brainstem, exercise central control in energy homeostasis. These centers house nuclei of neurons whose excitatory activity is sensitive to changes in glucose levels. Determining the different detection mechanisms, the phenotype of neurosecretion, and neural connections involving glucose-sensitive neurons is essential to understanding the response to hypoglycemia through modulation of food intake, thermogenesis, and activation of sympathetic and parasympathetic branches, inducing glucagon and epinephrine secretion and other hypothalamic-pituitary axis-dependent counterregulatory hormones, such as glucocorticoids and growth hormone. The aim of this review focuses on integrating the current understanding of various glucose-sensing mechanisms described in the brain, thereby establishing a relationship between neuroanatomy and control of physiological processes involved in both metabolic and energy balance. This will advance the understanding of increasingly prevalent diseases in the modern world, especially diabetes, and emphasize patterns that regulate and stimulate intake, thermogenesis, and the overall synergistic effect of the neuroendocrine system.

Pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in Sjögren syndrome: a double-blind randomized controlled trial.

BACKGROUND: Sjögren syndrome (SS) is associated with xerostomia and xerophthalmia. Pilocarpine has been shown to stimulate the secretion of saliva. OBJECTIVES: To investigate and compare the efficacy of pilocarpine and artificial saliva as symptomatic treatments for xerostomia and xerophthalmia in patients with SS. METHODS: A double-blind randomized controlled study was performed. A total of 72 patients with SS were assigned randomly to receive 10 drops of pilocarpine (5 mg) or 10 drops of artificial saliva orally, three times daily for 12 weeks. Whole saliva and tear flow were evaluated at baseline and periodically throughout the study to provide a global assessment of dryness and to report any adverse effects. RESULTS: Patients receiving pilocarpine had a statistically significant improvement in their salivary flow (P < 0·001), lacrimal flow (P < 0·001) and their subjective global assessment (P < 0·001), compared with patients who received artificial saliva. The most common side-effects were sialorrhoea and nausea. CONCLUSIONS: Pilocarpine is more effective than artificial saliva for enhancing salivary and lacrimal secretion in patients with SS. This is the first study to compare the efficacy of pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in SS.

Expression of a Novel Ciliary Protein, IIIG9, During the Differentiation and Maturation of Ependymal Cells.

IIIG9 is the regulatory subunit 32 of protein phosphatase 1 (PPP1R32), a key phosphatase in the regulation of ciliary movement. IIIG9 localization is restricted to cilia in the trachea, fallopian tube, and testicle, suggesting its involvement in the polarization of ciliary epithelium. In the adult brain, IIIG9 mRNA has only been detected in ciliated ependymal cells that cover the ventricular walls. In this work, we prepared a polyclonal antibody against rat IIIG9 and used this antibody to show for the first time the ciliary localization of this protein in adult ependymal cells. We demonstrated IIIG9 localization at the apical border of the ventricular wall of 17-day-old embryonic (E17) and 1-day-old postnatal (PN1) brains and at the level of ependymal cilia at 10- and 20-day-old postnatal (PN10-20) using temporospatial distribution analysis and comparing the localization with a ciliary marker. Spectral confocal and super-resolution Structured Illumination Microscopy (SIM) analysis allowed us to demonstrate that IIIG9 shows a punctate pattern that is preferentially located at the borders of ependymal cilia in situ and in cultures of ependymocytes obtained from adult rat brains. Finally, by immunogold ultrastructural analysis, we showed that IIIG9 is preferentially located between the axoneme and the ciliary membrane. Taken together, our data allow us to conclude that IIIG9 is localized in the cilia of adult ependymal cells and that its expression is correlated with the process of ependymal differentiation and with the maturation of radial glia. Similarly, its particular localization within ependymal cilia suggests a role of this protein in the regulation of ciliary movement.

Etapa de diagnóstico del Cáncer de Próstata ¿Estamos llegando a tiempo? / Prostate cancer stage at diagnosis. Are we running late?

INTRODUCCIÓN: El cáncer de próstata es el segundo cáncer más diagnosticado en hombres en Chile y el mundo. El tamizaje modificó la etapa de diagnóstico, siendo actualmente en EE.UU. un 80 por cinto localizada, 12 por cinto compromiso regional y 4 por ciento metastásico. Tamizaje con APE no está considerado dentro de un programa nacional en Chile. El objetivo de este estudio es caracterizar a la población diagnosticada de cáncer de próstata en un Hospital público en Chile. MATERIALES Y MÉTODO: Estudio descriptivo, retrospectivo. Se revisaron todas las fichas de los pacientes ingresados al GES por Cáncer de Próstata en el Hospital Carlos Van Buren de Valparaíso desde el año 2014 a 2016. RESULTADOS: Se revisaron 259 fichas y se analizaron 226. Edad promedio fue 70,5 años. 46 por ciento presentó APE sobre 20 ng/dL. 31 por ciento presentó metástasis. 42 por ciento recibió tratamiento paliativo. 57 por ciento se realizó tratamiento curativo, con edad promedio 67,4 años. De estos, 31,8 por ciento a cirugía, 68 por ciento índice Gleason <6 y 90 por ciento APE <20. 68 por ciento a RDT con o sin HT, 44 por ciento índice Gleason <6, 75 por ciento APE <20. DISCUSIÓN: El tamizaje del cáncer de próstata es un tema en discusión. En Chile no hay un programa nacional para realizar APE. Centros de atención primaria con acceso a APE tienen mayor tasa de tamizaje. La etapa al diagnóstico en nuestro centro difiere a las series de países desarrollados, siendo considerablemente superior la etapa metastásica. Esto podría deberse a la poca cobertura para detección temprana. Parece ser necesario implementar un programa nacional con cobertura de tamizaje para cáncer de próstata.(AU)

INTRODUCTION: Prostate cancer is the second most diagnosed cáncer in Chile and the world. Screening modified the stage at diagnosis, beeing now in the US 80 pertcent localized, 12 pertcent with regional compromised and 4 pertcent metastatic. Screening with PSA isn't considerd within a national program in Chile. The objetive of this study is to caracterize men diagnosed with prostate cancer at a public hospital in Chile. MATERIALS AND METHODS: Retrospective and descriptive study. Every patient who entered GES because of prostate cancer at the Carlos Van Buren Hospital from Valparaiso between 2014 and 2016 was review. RESULTS: 259 clinical records were review and 226 analized. Mean age was 70,5 years. 46 pertcent had PSA above 20 ng/dL. 31 % had metástasis. 42 % received paliative treatment. 57 % had curative treatment with a mean age of 67,4 years.From this group 31,8 pertcent surgery with a Gleason index <6 and 90 pertcent PSA <20. 68 pertcent had EBRT with or without HT, 44 pertcent of this group had Gleason index <6 and 75 pertcent PSA <20. DISCUSSION: Prostate cancer screening it's a debated topic. In Chile there's no national program to do a PSA. Primary care centers with acces to PSA have more rate of screening. Stage at diagnosis in our center difers from developed countries series, beeing metastatic stage considerably superior. This could be because of the low screening rate for early diagnosis. It seems necesary to implement a national program for prostate cancer screening.(AU)

[Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy]. / Ergotismo por uso simultáneo de ergotamínico y terapia antirretroviral: Report of one case.

High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results.

Ergotismo por uso simultáneo de ergotamínico y terapia antirretroviral: Report of one case / Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy

High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results.

Mente Activa® Improves Impaired Spatial Memory in Aging Rats.

OBJECTIVES: Aging is accompanied by a decline in several aspects of the cognitive function, having negative personal and socioeconomic impacts. Dietary supplements could be beneficial for preventing age-related cognitive decline. In this context, we examined whether the nutritional supplement Mente Activa® has beneficial effects on aging-related cognitive deficits without inducing side effects. METHODS: Mente Activa® was administered to old rats (n= 30 treated rats and n= 30 control rats) during 5 months, and the Morris water maze was used to test the learning capacities of the animals. The first assessment was conducted before the nutritional intervention (age of 18-19 months), to determine the baseline of the performance of animals on this test, and the second assessment was performed at the end of the treatment (23-24 moths). In order to examine possible secondary effects of this nutritional supplement, plasma, heart anatomy and liver parameters were evaluated. RESULTS: Our data indicate that supplemented rats showed less escape latency, distance swum, higher use of spatial search strategies, and crossed the former platform location with higher frequency than control rats. These effects were specific of the treatment, indicating that this nutritional supplement has a beneficial effect on spatial memory. On the other hand, the regular intake of Mente Activa® did not induce any negative effects in plasma parameters and heart size. CONCLUSIONS: Aged rats under a sustained dietary intake of the nutritional supplement Mente Activa® displayed improved learning and memory abilities compared to the non-treated rats. These results suggest the therapeutic potential and safety of use of Mente Activa® for age-related cognitive deficits, particularly, in the onset of the first cognitive dysfunction symptoms.

Selective inactivation of NADPH oxidase 2 causes regression of vascularization and the size and stability of atherosclerotic plaques.

BACKGROUND: A variety of NADPH oxidase (Nox) isoforms including Noxs 1, 2, 4 and 5 catalyze the formation of reactive oxygen species (ROS) in the vascular wall. The Nox2 isoform complex has arguably received the greatest attention in the progression of atherogenesis in animal models. Thus, in the current study we postulated that specific Nox2 oxidase inhibition could reverse or attenuate atherosclerosis in mice fed a high-fat diet. METHODS: We evaluated the effect of isoform-selective Nox2 assembly inhibitor on the progression and vascularization of atheromatous plaques. Apolipoprotein E-deficient mice (ApoE-/-) were fed a high fat diet for two months and treated over 15 days with Nox2ds-tat or control sequence (scrambled); 10 mg/kg/day, i.p. Mice were sacrificed and superoxide production in arterial tissue was detected by cytochrome C reduction assay and dihydroethidium staining. Plaque development was evaluated and the angiogenic markers VEGF, HIF1-α and visfatin were quantified by real time qRT-PCR. MMP-9 protein release and gelatinolytic activity was determined as a marker for vascularization. RESULTS: Nox2ds-tat inhibited Nox-derived superoxide determined by cytochrome C in carotid arteries (2.3 ± 0.1 vs 1.7 ± 0.1 O2(•-) nmol/min*mg protein; P < 0.01) and caused a significant regression in atherosclerotic plaques in aorta (66 ± 6 µm(2) vs 37 ± 1 µm(2); scrmb vs. Nox2ds-tat; P < 0.001). Increased VEGF, HIF-1α, MMP-9 and visfatin expression in arterial tissue in response to high-fat diet were significantly attenuated by Nox2ds-tat which in turn impaired both MMP-9 protein expression and activity. CONCLUSION: Given these results, it is quite evident that selective Nox inhibitors can reverse vascular pathology arising with atherosclerosis.

Job strain and cognitive decline: a prospective study of the framingham offspring cohort.

BACKGROUND: Workplace stress is known to be related with many behavioral and disease outcomes. However, little is known about its prospective relationship with measures of cognitive decline. OBJECTIVE: To investigate the association of job strain, psychological demands and job control on cognitive decline. METHODS: Participants from Framingham Offspring cohort (n=1429), were assessed on job strain, and received neuropsychological assessment approximately 15 years and 21 years afterwards. RESULTS: High job strain and low control were associated with decline in verbal learning and memory. Job strain was associated with decline in word recognition skills. Active job and passive job predicted decline in verbal learning and memory relative to low strain jobs in the younger subgroup. Active job and demands were positively associated with abstract reasoning skills. CONCLUSIONS: Job strain and job control may influence decline in cognitive performance.

Large electric-field-induced strain in centrosymmetric crystals of a dipolar ruthenium alkynyl complex.

Dipolar molecular crystals present different physical properties from traditionally strongly correlated ionic solid-state inorganic crystals due to the weak intermolecular bonding. Herein, centrosymmetric dipolar molecular crystals of the organoruthenium complex trans-[Ru(C≡CC6H4-4-NO2)(C≡CPh)(dppe)2] [dppe = 1,2-bis(diphenylphosphino)ethane] display a large electric-field-induced strain behaving differently from conventional piezoelectric materials that must, structurally, be noncentrosymmetric. Further studies of related systematically varied crystalline organoruthenium complexes reveal that the strong electromechanical coupling effect is not from classical ferroelectricity, electrostriction, flexoelectricity or electrochemical strain. It is, instead, attributed to the disorder in the molecular packing, which facilitates reorientation of the molecular dipoles under the action of an applied electric field. This provides a fresh insight into the design and development of new functional materials and a promising source of electromechanical coupling in organometallic, and more generally dipolar molecular, crystals.

Resultados en salud a largo plazo de un programa estructurado de rehabilitación respiratoria en pacientes con enfermedad pulmonar obstructiva crónica / Long-term health results of a structured respiratory rehabilitation program in patients with COPD

Introducción. La enfermedad pulmonar obstructiva crónica (EPOC) constituye una patología de gran impacto en nuestra sociedad siendo la disnea el síntoma principal. Los programas de rehabilitación respiratoria pretenden disminuir la morbimortalidad y aumentar la calidad de vida. Nuestro objetivo es analizar la efectividad a largo plazo de un programa de rehabilitación respiratoria en cuanto a calidad de vida, adherencia al tratamiento y morbimortalidad. Material y métodos. Estudio observacional transversal sobre una cohorte prospectiva. Incluye a pacientes con EPOC grado III y IV de GOLD estabilizados que han completado el programa de rehabilitación respiratoria. Se diseña un cuestionario recogiendo percepción de disnea, aparición de exacerbaciones, mortalidad, adherencia al tratamiento y calidad de vida medidas con los cuestionarios ansiedad-depresión, Saint George Respiratory Questionnaire (SGRQ) y Chronic Respiratory Questionary (CRQ) al inicio y al año del tratamiento. Resultados. Se aprecia disminución de la percepción de disnea al mes del tratamiento. La media del número de exacerbaciones fue 4,06 y el porcentaje de mortalidad del 5,9% al año de tratamiento. Un 78,9% de pacientes continuaron el entrenamiento domiciliario, obteniéndose mejores resultados al realizarlo más de 3 días en semana. La media de la mejoría de calidad de vida fue positiva en los cuestionarios ansiedad/depresión, en la escala SGRQ y en algunas áreas de la escala CRQ. Conclusiones. La intervención sanitaria centrada en un programa de rehabilitación respiratoria es útil a largo plazo para el beneficio en salud, observándose una mejoría en la autonomía para las actividades de la vida diaria y en la autopercepción de calidad de vida (AU)

Introduction. Chronic obstructive pulmonary disease (COPD) has a huge impact in Spain. The main symptom is dyspnea. Pulmonary rehabilitation aims to decrease morbidity and mortality and increase quality of life. The aim of our study was to assess the long-term effectiveness of a respiratory rehabilitation program in enhancing quality of life and treatment adherence and in reducing mortality and morbidity. Material and methods. A cross-sectional observational study was carried out in a prospective cohort of patients with stable grade III and IV COPD, as measured by the GOLD scale. The participants completed a pulmonary rehabilitation program. A questionnaire was designed to collect perceptions of dyspnea, exacerbations, mortality, treatment adherence, and quality of life, measured with anxiety-depression questionnaires, the Saint George Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Questionnaire (CRQ) before and 1 year after of treatment. Results. The perception of dyspnea decreased after a month of treatment. At 1 year, the number of exacerbations was 4.06 and mortality was 5.9%. A total of 78.9% of the patients continued training at home and obtained better results if they trained 3 days per week or more. Quality of life showed improvement in the anxiety-depression questionnaires, SGRQ scale, and in some areas of the CRQ scale. Conclusions. The pulmonary rehabilitation program produced long-term benefits for health, improving autonomy in activities of daily living and self-perceived quality of life (AU)