Functional Status of Patients over 65 Years Old Intervened on for a Hip Fracture One Year after the Operation.

OBJECTIVES: Evaluation of the functional status one year after a hip fracture surgery and the influence of sarcopenia and other clinical factors at the time of admission. METHOD: Prospective observational study with 135 patients over 65 years of age. Functional status of basic (modified Katz) and instrumental activities (Lawton and Brody) and walking ability (Functional Ambulation Classification, FAC) was measured on admission, at discharge, and telephonically one year later. The risk or positive screening of sarcopenia (SARC-F) and cognitive status (Pfeiffer), as well as clinical variables, were evaluated. RESULTS: 72% of patients are women; 36% have a risk of sarcopenia (Sarc-F ≥ 4), and 43% have moderate-severe cognitive impairment (Pfeiffer ≥ 5). Walking capacity at one year was closer to the values at admission more often in women than in men (0.2 ± 1.3 points vs. 0.9 ± 1.6; p = 0.001), as well as in patients without risk of sarcopenia versus sarcopenic patients (0.3 ± 1.2 points vs. 0.7 ± 1.7; p = 0.001), although their evolution did not show significant differences (p = 0.183). Instrumental activities after one year have not been recovered (1.7 ± 2.5 points; p = 0.032), and patients at risk of sarcopenia showed worse values (1.7 ± 1.9 points vs. 3.7 ± 2.7; p < 0.001) and worse evolution (p = 0.012). The evolution of basic activities varied according to the risk of sarcopenia (0.6 ± 1.4 points vs. 1.4 ± 2.1; p = 0.008). CONCLUSIONS: Functional status at one year is related to the functional status at admission, the positive screening of sarcopenia, sex, and cognitive impairment of the patient. Knowing at the time of admission an estimate of the functional status at one year will help to reinforce the individual treatment of patients with a worse prognosis.

Increase of oxidation and inflammation in nervous and immune systems with aging and anxiety.

According to the oxidation-inflammation theory of aging, chronic oxidative stress and inflammatory stress situations (with higher levels of oxidant and inflammatory compounds and lower antioxidant and anti-inflammatory defenses) are the basis of the agerelated impairment of organism functions, including those of the nervous and immune systems, as well as of the neuroimmune communication, which explains the altered homeostasis and the resulting increase of morbidity and mortality. Overproduction of oxidant compounds can induce an inflammatory response, since oxidants are inflammation effectors. Thus, oxidation and inflammation are interlinked processes and have many feedback loops. However, the nature of their potential interactions, mainly in the brain and immune cells, and their key involvement in aging remain unclear. Moreover, in the context of the neuroimmune communication, it has been described that an oxidative-inflammatory situation occurs in subjects with anxiety, and this situation contributes to an immunosenescence, alteration of survival responses and shorter life span. As an example of this, a model of premature aging in mice, in which animals show a poor response to stress and high levels of anxiety, an oxidative stress in their immune cells and tissues, as well as a premature immunosenescence and a shorter life expectancy, will be commented in the present review. This model supports the hypothesis that anxiety can be a situation of chronic oxidative stress and inflammation, especially in brain and immune cells, and this accelerates the rate of aging.

Functional impairment as a defining feature of: amnestic MCI cognitive, emotional, and demographic correlates.

BACKGROUND: Early definitions of mild cognitive impairment (MCI) excluded the presence of functional impairment, with preservation of a person's ability to perform activities of daily living (ADL) as a diagnostic criterion. However, recent studies have reported varying degrees of functional impairment associated with MCI. Hence, we aimed to test the potential functional impairment associated with MCI and its predictors. METHODS: Sixty-nine healthy elderly subjects, 115 amnestic single-domain MCI subjects (a-MCI), and 111 amnestic multi-domain MCI subjects (md-MCI) were assessed using a battery of neuropsychological tests including measures of attention, memory, working memory, executive functions, language, and depression. Additionally, functional ability was assessed by both qualitative (WHO-DAS II) and quantitative (CHART) instruments. Cognitive and functional performance was compared between groups, and regression analyses were performed to identify predictors of functional ability. RESULTS: The md-MCI group was more impaired than the a-MCI group, and both were more impaired than healthy subjects in all cognitive measures, in total CHART score, CHART cognitive and mobility subscores, and WHO-DAS II communication and participation subscales. For the rest of the functional measures, the md-MCI group was more impaired than healthy controls. Prediction of functional ability by cognitive measures was limited to md-MCI subjects and was higher for the CHART than for the WHO-DAS II. The WHO-DAS II was largely influenced by depressive symptoms. CONCLUSIONS: Functional impairment is a defining feature of MCI and is partially dependent on the degree of cognitive impairment. Quantitative measures of functional ability seem more sensitive to functional impairment in MCI than qualitative measures, which seem to be more related to depression.

Age-related changes in xanthine oxidase activity and lipid peroxidation, as well as in the correlation between both parameters, in plasma and several organs from female mice

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Xanthine oxidase, a purine catabolism enzyme, has been implicated as an important source of oxidant production and plays an essential role in several inflammatory and oxidative stress-related diseases. It is known that the increasing levels of oxidants cause the chronic oxidative stress characteristic of the ageing process. The aim of the present work was to determine the changes in xanthine oxidase activity and oxidative damage to lipids in several organs (liver, kidney, spleen, lung and two different brain areas, namely cerebral cortex and brainstem) and plasma from two different age groups of BALB/c female mice: adult (7-month-old) and old (18-month-old) mice, as well as to analyse the possible correlation between both parameters. Xanthine oxidase activity was significantly increased in liver, cerebral cortex and plasma from old mice in comparison with adults. Similar results were obtained in the lipid peroxidation levels, in which old mice showed a high increment in liver and cerebral cortex. Moreover, the results show a significant and positive correlation between xanthine oxidase activity and lipid peroxidation levels in cerebral cortex. The age-related increase in the xanthine oxidase activity and lipid peroxidation in liver and cerebral cortex of mice seems to suggest that the xanthine oxidase plays a role in the acceleration of the oxidative damage in these organs with age and its possible contribution to the pathophysiological changes associated to the process of ageing (AU)

Age-related changes in xanthine oxidase activity and lipid peroxidation, as well as in the correlation between both parameters, in plasma and several organs from female mice.

Xanthine oxidase, a purine catabolism enzyme, has been implicated as an important source of oxidant production and plays an essential role in several inflammatory and oxidative stress-related diseases. It is known that the increasing levels of oxidants cause the chronic oxidative stress characteristic of the ageing process. The aim of the present work was to determine the changes in xanthine oxidase activity and oxidative damage to lipids in several organs (liver, kidney, spleen, lung and two different brain areas, namely cerebral cortex and brainstem) and plasma from two different age groups of BALB/c female mice: adult (7-month-old) and old (18-month-old) mice, as well as to analyse the possible correlation between both parameters. Xanthine oxidase activity was significantly increased in liver, cerebral cortex and plasma from old mice in comparison with adults. Similar results were obtained in the lipid peroxidation levels, in which old mice showed a high increment in liver and cerebral cortex. Moreover, the results show a significant and positive correlation between xanthine oxidase activity and lipid peroxidation levels in cerebral cortex. The age-related increase in the xanthine oxidase activity and lipid peroxidation in liver and cerebral cortex of mice seems to suggest that the xanthine oxidase plays a role in the acceleration of the oxidative damage in these organs with age and its possible contribution to the pathophysiological changes associated to the process of ageing.

Consultas de viajes internacionales en Palencia / Consultations on international travel in Palencia

Objetivos: estudiar las características de las consultas realizadasen la Unidad de Viajes Internacionales de Palenciadurante el año 2004 y describir el grado de cumplimiento delas recomendaciones preventivas, los efectos adversos referidosdespués de la administración de vacunas y quimioprofilaxisantipalúdica y los problemas de salud que los viajerosrefirieron en su viaje.Material y métodos: estudio observacional descriptivotransversal. Los datos se obtuvieran mediante dos encuestas(personal antes del viaje y telefónica después del viaje) querecogían variables sociodemográficas, características del viaje,estado de salud, vacunaciones previas, recomendacionespreventivas y cumplimiento de éstas, efectos adversos postvacunalesy postquimioprofilaxis antipalúdica, coste del tratamientopreventivo y problemas de salud acontecidos duranteel viaje. Los resultados se expresaron medianteestadística descriptiva y se utilizó el test de Ji Cuadrado parala comparación de variables cualitativas. Se calcularon OddsRatios y sus intervalos de confianza al 95%.Resultados: se atendieron 596 viajeros durante 2004. Seconsiguió contactar telefónicamente con 474 después delviaje (79%). El continente mayoritariamente elegido por losviajeros fue el latinoamericano (41%) y el 60% decidió realizarsu viaje organizado. La vacuna contra tétanos-difteria(50,4%) y la mefloquina (Lariam®) (55,9%), fueron la vacunay el antipalúdico más recomendados, respectivamente. Losefectos secundarios a la toma de antipalúdicos fueron máscomunes con la mefloquina (un 67,8%). El 40,3% de losviajeros tuvo problemas de salud durante el viaje y el 20,3%al regreso del mismo. La diarrea (44,5%) fue el síntoma másfrecuentemente referido durante el viaje debido, en un 25%,a la alimentación.Conclusiones: es necesaria la visita a una Unidad de ViajesInternacionales con tiempo suficiente de antelación a la realizacióndel viaje para la toma de medidas preventivas. Lamayoría de los viajeros siguieron los consejos recomendados,siendo el problema de salud más frecuente la diarrea

Objectives: to study the characteristics of the consultationsmade at the International Travel Unit of Palencia in 2004and to describe the extent of adhesion/compliance to preventiverecommendations, the adverse effects reported afterthe administration of vaccines and antipaludic chemoprophylaxisand the health problems reported by travellersin their journeys.Material and methods: cross-sectional descriptive observationalstudy. Data were obtained by means of two polls (apersonal interview before the trip and a telephone interviewafter the trip) which compiled sociodemographic variables,characteristics of the trip, previous vaccinations, preventiverecommendations and their compliance, post vaccine adverseeffects, antipaludic post chemoprophylaxes, costs of thepreventive treatment and health problems that occurredduring the trip. The results were analysed by descriptive statisticsand the Chi square test for the comparison of variables.Odds Ratios and their interval confidence intervalswere calculated at 95%.Results: 596 travellers were attended in 2004. 474 (79%)were reached on the telephone after the trip. The SouthAmerican continent was chosen by the majority of travellers(41%) and 60% decided for an organised trip. Vaccinationagainst tetanus/diphtheria (50,4%) and mefloquine(Lariam®) (55,9%) were the most recommended vaccine andantipaludic agent, respectively.Side effects secondary to the intake of antipaludic agentswere more common with mefloquine (67,8%). 40,3% ofthe travellers had health problems during their trip and 20,3upon their return. Diarrhoea (44,5%) was the most commonlyreferred health problem during their journey due tothe food they ate in 25% of subjects.Conclusions: people intending to travel should visit the InternationalTravel Unit with sufficient time in advance to takethe necessary precautions and get advice. Most travellersfollowed the recommendations given to them, being diarrhoea the most common problem (AU)

Proepithelin promotes migration and invasion of 5637 bladder cancer cells through the activation of ERK1/2 and the formation of a paxillin/FAK/ERK complex.

The growth factor proepithelin (also known as progranulin, acrogranin, PC-derived growth factor, or granulin-epithelin precursor) is a secreted glycoprotein that functions as an important regulator of cell growth, migration, and transformation. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian, and renal cancer as well as glioblastomas. In this study, we have investigated the effects of proepithelin on bladder cancer cells using human recombinant proepithelin purified to homogeneity from 293-EBNA cells. Although proepithelin did not appreciably affect cell growth, it did promote migration of 5637 bladder cancer cells and stimulate in vitro wound closure and invasion. These effects required the activation of the mitogen-activated protein kinase pathway and paxillin, which upon proepithelin stimulation formed a complex with focal adhesion kinase and active extracellular signal-regulated kinase. Our results provide the first evidence for a role of proepithelin in stimulating migration and invasion of bladder cancer cells, and support the hypothesis that this growth factor may play a critical role in the establishment of the invasive phenotype.

BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan.

Endorepellin, the C-terminal domain of the heparan sulfate proteoglycan perlecan, possesses angiostatic activity. The terminal laminin-like globular (LG3) domain of endorepellin appears to possess most of the biological activity on endothelial cells. LG3 protein has been detected in the urine of patients with end-stage renal disease and in the amniotic fluid of pregnant women with premature rupture of fetal membranes. These findings suggest that proteolytic processing of endorepellin and the generation of LG3 might have biological significance. In this study, we have identified specific enzymes of the bone morphogenetic protein-1 (BMP-1)/Tolloid family of metalloproteases that cleave LG3 from recombinant endorepellin at the physiologically relevant site and that cleave LG3 from endogenous perlecan in cultured mouse and human cells. The BMP-1/Tolloid family of metalloproteases is thereby implicated in the processing of a major basement membrane proteoglycan and in the liberation of an anti-angiogenic factor. Using molecular modeling, site-directed mutagenesis and angiogenic assays, we further demonstrate that LG3 activity requires specific amino acids involved in Ca(2+) coordination.

Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha2beta1 integrin.

Endorepellin, the COOH-terminal domain of the heparan sulfate proteoglycan perlecan, inhibits several aspects of angiogenesis. We provide evidence for a novel biological axis that links a soluble fragment of perlecan protein core to the major cell surface receptor for collagen I, alpha2beta1 integrin, and provide an initial investigation of the intracellular signaling events that lead to endorepellin antiangiogenic activity. The interaction between endorepellin and alpha2beta1 integrin triggers a unique signaling pathway that causes an increase in the second messenger cAMP; activation of two proximal kinases, protein kinase A and focal adhesion kinase; transient activation of p38 mitogen-activated protein kinase and heat shock protein 27, followed by a rapid down-regulation of the latter two proteins; and ultimately disassembly of actin stress fibers and focal adhesions. The end result is a profound block of endothelial cell migration and angiogenesis. Because perlecan is present in both endothelial and smooth muscle cell basement membranes, proteolytic activity during the initial stages of angiogenesis could liberate antiangiogenic fragments from blood vessels' walls, including endorepellin.

A novel interaction between perlecan protein core and progranulin: potential effects on tumor growth.

In an in vivo search of novel partners for perlecan, a major heparan sulfate proteoglycan of basement membranes and cell surfaces, we identified progranulin, a secreted growth factor, as a strong interacting protein. Unambiguous interaction, first observed with the yeast two-hybrid system, was corroborated by co-immunoprecipitation studies using cell-free transcription/translation and transient cell transfection assays. The interaction of progranulin with perlecan domain V involved the first two laminin- and epidermal growth factor-like repeats. Within progranulin, the subdomains interacting most with perlecan harbored granulins F and B. Kinetics analysis of the interaction using surface plasmon resonance showed a saturable binding of relative low affinity (KD approximately 1 microM). These results were supported by significant expression overlap of these two proteins in a series of ovarian tumor tissue microarrays. Progranulin was present within proliferating blood vessels of ovarian carcinomas and perivascular matrices, with a distribution similar to perlecan. Notably, both progranulin and domain V stimulated the growth of adrenal carcinoma cells. However, when used together in equimolar amounts, the two proteins counteracted each other's activity. Thus, progranulin/perlecan interaction could contribute to a fine regulation of tumor angiogenesis and could ultimately affect cancer growth.

Influence of the 3D-conformation, glycan component and microheterogeneity on the epitope structure of Ole e 1, the major olive allergen. Use of recombinant isoforms and specific monoclonal antibodies as immunological tools.

Ole e 1 is the main allergen of olive pollen, which is a major cause of pollinosis in countries of the Mediterranean area. Nine Ole e 1-specific murine monoclonal antibodies (mAbs), as well as two Ole e 1-isoforms and two Ole e 1-like allergens from lilac and privet, all of them obtained in Pichia pastoris by recombinant methods, have been used as tools to determine the role of the three-dimensional (3D)-folding, the glycan component and several point changes of the amino acid sequence in the binding of murine IgG mAbs and human IgE to the olive allergen. Seven mAb families (F1-F7) were established, two of which (F1 and F2) recognize continuous epitopes. The carbohydrate moiety of Ole e 1 was involved in the binding to F2 and F4, whereas F3 and F7 were able to bind to all Ole e 1 variants. The remaining families of IgG murine antibodies exhibited different affinities for the antigens assayed in a native or denatured conformation. Although the binding of human IgE to Ole e 1 was not affected by heat treatment, it was shown to be strongly dependent on the integrity of the disulfide bridges and was partially inhibited by F3-F7 IgG antibodies, their individual values ranging from 12 to 31% and reaching 53% with their mixture. The IgE from sera of olive-allergic patients showed a significant diversity of binding capacity to the members of the Ole e 1-like family due to the microheterogeneity of their polypeptide sequences, in spite of their highly conserved primary structures. Whereas one of the isoforms of Ole e 1 exhibits a highly similar behavior to the natural form, being a putative molecule for diagnostic purposes, other ones can be considered as hypoallergenic variants of this allergen and, thus, potential candidates to be used in immunotherapy.