Next generation sequencing characterizes the extent of HLA diversity in an Argentinian registry population.

Next generation DNA sequencing is used to determine the HLA-A, -B, -C, -DRB1, and -DQB1 assignments of 1472 unrelated volunteers for the unrelated donor registry in Argentina. The analysis characterized all HLA exons and introns for class I alleles; at least exons 2, 3 for HLA-DRB1; and exons 2 to 6 for HLA-DQB1. Of the distinct alleles present, there are 330 class I and 98 class II. The majority (~98%) of the cumulative allele frequency at each locus is contributed by alleles that appear at a frequency of at least 1 in 1000. Fourteen (18.2%) of the 77 novel class I and II alleles carry nonsynonymous variation within their exons; 52 (75.4%) class I novel alleles carry only single, apparently random, nucleotide variation within their introns/untranslated regions. Alleles encoding protein variation not usually detected by typing focused only on the exons encoding the antigen recognition domain are 1.0% of the class I assignments and 7.3% of the class II assignments (predominantly DQB1*02:02:01, DQB1*03:19:01, and DRB1*14:54:01). Updates to the common and well documented list of alleles include 10 alleles previously thought to be uncommon but that are found at least 30 times. Five locus haplotypes estimated using the expectation-maximization algorithm as present 3 or more times total 187. While the known HLA diversity continues to increase, the conservation of known allele sequences is remarkable. Overall, the HLA diversity observed in the Argentinian population reflects its European and Native American ancestry.

Full 3-D OCT-based pseudophakic custom computer eye model.

We compared measured wave aberrations in pseudophakic eyes implanted with aspheric intraocular lenses (IOLs) with simulated aberrations from numerical ray tracing on customized computer eye models, built using quantitative 3-D OCT-based patient-specific ocular geometry. Experimental and simulated aberrations show high correlation (R = 0.93; p<0.0001) and similarity (RMS for high order aberrations discrepancies within 23.58%). This study shows that full OCT-based pseudophakic custom computer eye models allow understanding the relative contribution of optical geometrical and surgically-related factors to image quality, and are an excellent tool for characterizing and improving cataract surgery.

A CCL chemokine-derived peptide (CDIP-2) exerts anti-inflammatory activity via CCR1, CCR2 and CCR3 chemokine receptors: Implications as a potential therapeutic treatment of asthma.

Allergic asthma is a chronic inflammatory disease characterized by the accumulation of eosinophils, Th2 cells and mononuclear cells in the airways, leading to changes in lung architecture and subsequently reduced respiratory function. We have previously demonstrated that CDIP-2, a chemokine derived peptide, reduced in vitro chemotaxis and decreased cellular infiltration in a murine model of allergic airway inflammation. However, the mechanisms involved in this process have not been identified yet. Now, we found that CDIP-2 reduces chemokine-mediated functions via interactions with CCR1, CCR2 and CCR3. Moreover, using bone marrow-derived eosinophils, we demonstrated that CDIP-2 modifies the calcium fluxes induced by CCL11 and down-modulated CCR3 expression. Finally, CDIP-2 treatment in a murine model of OVA-induced allergic airway inflammation reduced leukocyte recruitment and decreases production of cytokines. These data suggest that chemokine-derived peptides represent new therapeutic tools to generate more effective antiinflammatory drugs.

Optimización del uso de las imágenes en la patología suprarrenal (parte 2)q

Objetivos de aprendizaje: El objetivo de este trabajo es proponer un algoritmo de estudio por imágenes de las lesiones suprarrenales que permita arribar a un diagnóstico correcto en el menor tiempo posible. Esto favorece la adopción de la conducta terapéutica más apropiada para cada patología y puede modifi car en forma sustancial el tratamiento. Aunque las características estructurales de las lesiones generalmente son inespecífi cas, es posible, a través de las técnicas de imágenes actuales, diferenciar las lesiones compatibles con procesos benignos de las compatibles con procesos malignos y, con la colaboración del endocrinólogo y el laboratorio, también se pueden distinguir las lesiones funcionantes de las no funcionantes. Revisión de tema: Se evaluaron en forma retrospectiva, entre mayo del 2009 y diciembre del 2011, 157 pacientes con patología suprarrenal. En total, eran 95 mujeres y 61 hombres, de 33 a 78 años (media: 55 años). El protocolo de estudio consistió en una tomografía computada (TC) sin contraste intravenoso (IV), con toma de la densidad de la lesión, seguida de una tomografía computada con contraste intravenoso y tiempo de lavado con toma de densidad de la lesión en tiempo portal y tardío a los 15 minutos (tiempo de lavado o wash-out). Las mediciones y cálculos realizados fueron: tamaño de la lesión suprarrenal, densidad media de la misma durante las tres fases estudiadas y porcentajes de lavado relativo y absoluto. Se realizó resonancia magnética (RM) y tomografía computada por emisión de positrones con 18F-fl uorodesoxiglucosa (FDG-PET/TC) sólo en aquellos pacientes que así lo requirieron. Además, se compararon los resultados con los de la literatura actualizada sobre el tema. Hallazgos en imágenes: La conjunción de los datos clínicos, de laboratorio y las imágenes con el algoritmo propuesto permitió identifi car 59 adenomas no funcionantes (49 unilaterales y 10 bilaterales), 29 adenomas funcionantes, 9 hiperplasias bilaterales, 4 mielolipomas (2 de ellos en una paciente con hiperplasia suprarrenal congénita virilizante simple), 2 quistes, 2 hematomas, 3 linfomas (2 secundarios y 1 primario bilateral), 30 metástasis, 5 carcinomas adrenocorticales, 12 feocromocitomas, 1 feocromocitoma maligno y 1 ganglioneuroma. Conclusión: La utilización de un algoritmo de estudio adecuado, con las herramientas diagnósticas más apropiadas y accesibles, permite la correcta caracterización de las lesiones suprarrenales. A su vez, evita la pérdida de tiempo, el diagnóstico incorrecto, la irradiación excesiva del paciente y la mala utilización de los recursos.

Training Objectives: The aim of this study is to propose an algorithm for the evaluation of adrenal lesions in order to arrive at the correct diagnosis in the shortest possible time. This method would be suitable for the most appropriate therapeutic procedures for each pathology, and may substantially modify a given treatment. In spite of the fact that the structural features of lesions are generally non-specifi c, with imaging techniques, it is possible to establish features which could help us differentiate benign from malignant lesions and with the contribution of the endocrinologist and the laboratory, to distinguish functional from non-functional ones. Topic review: A retrospective evaluation from May 2009 to December 2011 has been carried out on 157 patients with adrenal diseases, including 95 females and 61 males, from 33 to 78 years of age (mean age 55). The study protocol consisted in non-contrasted intravenous computed tomography, with lesion density measurement, followed by contrasted intravenous computed tomography and wash out time with lesion density determination in portal time and delayed after 15 minutes wash out. Measurements and calculations were: adrenal lesion size, medium density and absolute and relative wash-out percentiles. Magnetic resonance and 18F-fl uorodeoxyglucose positron emission tomography was only performed on those patients that required these techniques. A comparison of the present results with those in the literature is included. Imaging fi ndings: Fifty-nine patients with a non-functional adenoma were identifi ed (49 unilateral and 10 bilateral), 29 functional adenomas, 9 with bilateral hyperplasia, 4 myelolipomas (2 in a female patient with simple virilizing congenital adrenal hyperplasia), 2 cysts, 2 hematomas, 3 lymphomas (2 secondary and 1 primary bilateral), 30 metastases, 5 adrenocortical carcinomas, 12 pheochromocytoma,1 malignant pheochromocytoma and 1 ganglioneuroma. Conclusion: The use of an appropriate study algorithm, with proper diagnostic tools, enables adrenal lesions to be correctly differentiated. Moreover, this approach prevents loss of time, a wrong diagnosis, excessive irradiation of the patient, and incorrect use of resources.

Optimización del uso de las imágenes en la patología suprarrenal (parte 1) / Optimization of the use of imaging in adrenal pathology (part 1)

Objetivos de aprendizaje: El objetivo de este trabajo es proponer un algoritmo de estudio por imágenes de las lesiones suprarrenales que permita arribar a un diagnóstico correcto en el menor tiempo posible. Esto favorece la adopción de la conducta terapéutica más apropiada para cada patología y puede modificar en forma sustancial un tratamiento. Aunque las características estructurales de las lesiones generalmente son inespecíficas, es posible, a través de las técnicas de imágenes actuales, diferenciar las lesiones compatibles con procesos benignos de las compatibles con procesos malignos y, con la colaboración del endocrinólogo y el laboratorio, también se pueden distinguir las lesiones funcionantes de las no funcionantes. Revisión de tema: Se evaluaron en forma retrospectiva, entre mayo del 2009 y diciembre del 2011, 157 pacientes con patología suprarrenal. En total, eran 95 mujeres y 61 hombres, de 33 a 78 años (media: 55 años). El protocolo de estudio consistió en una tomografía computada (TC) sin contraste intravenoso (IV), con toma de la densidad de la lesión, seguida de una tomografía computada con contraste intravenoso y tiempo de lavado con toma de densidad de la lesión en tiempo portal y tardío a los 15 minutos (tiempo de lavado o wash-out). Las mediciones y cálculos realizados fueron: tamaño de la lesión suprarrenal, densidad media de la misma durante las tres fases estudiadas y porcentajes de lavado relativo y absoluto. Se realizó resonancia magnética (RM) y tomografía computada por emisión de positrones con 18F-fluorodesoxiglucosa (FDG-PET/TC) sólo en aquellos pacientes que así lo requirieron. Además, se compararon los resultados con los de la literatura actualizada sobre el tema. Hallazgos en imágenes: La conjunción de los datos clínicos, de laboratorio y las imágenes con el algoritmo propuesto permitió identificar 59 adenomas no funcionantes (49 unilaterales y 10 bilaterales), 29 adenomas funcionantes, 9 hiperplasias bilaterales, 4...

Objectives of training: The aim of this study is to propose an algorithm for the evaluation of adrenal lesions in order to arrive at the correct diagnosis in the shortest possible time.This method would favor the most appropriate therapeutic procedures for each pathology and may substantially modifi ed a given treatment. In spite of the fact that the structural features of lesions are generally non-specifi c, it is possible with imaging techniques, to establish compatible features which could help us differentiate benign from malignant lesions and with the contribution of the endocrinologist and the laboratory, to distinguish functional from non-functional ones.Topic revision: A retrospective evaluation was carried out from May 2009 to December 2011 on 157 patients with adrenal diseases, including 95 females and 61 males, from 33 to 78 years of age (mean age 55). The study protocol consisted of non-contrasted intravenous computed tomography, with lesion density measurement, followed by contrasted intravenous computed tomography and wash out time with lesion density determination in portal time and later at 15’ during wash out.Measurements and calculations were: adrenal lesion size, medium density and absolute and relative washing percentiles. Magnetic resonance and 18F-fl uorodesoxyglucose positron emission tomography was only performed on those patients who required these techniques. A comparison of the present results with those in the literature is included.Imaging fi ndings: Fifty-nine patients with non-functional adenoma were identifi ed (49 unilateral and 10 bilateral), 29 functional adenomas, 9 with bilateral hyperplasia, 4 myelolipomas (2 in a female patient with simple virilizing congenital adrenal hyperplasia), 2 cysts, 2 hematomas, 3 lymphomas (2 secondary and 1 primary bilateral), 30 metastases, 5 adrenocortical carcinomas, 12 pheochromocytomas,1 malignant pheochromocytoma, and 1 ganglioneuroma...

Optimización del uso de las imágenes en la patología suprarrenal (parte 1) / Optimization of the use of imaging in adrenal pathology (part 1)

Objetivos de aprendizaje: El objetivo de este trabajo es proponer un algoritmo de estudio por imágenes de las lesiones suprarrenales que permita arribar a un diagnóstico correcto en el menor tiempo posible. Esto favorece la adopción de la conducta terapéutica más apropiada para cada patología y puede modificar en forma sustancial un tratamiento. Aunque las características estructurales de las lesiones generalmente son inespecíficas, es posible, a través de las técnicas de imágenes actuales, diferenciar las lesiones compatibles con procesos benignos de las compatibles con procesos malignos y, con la colaboración del endocrinólogo y el laboratorio, también se pueden distinguir las lesiones funcionantes de las no funcionantes. Revisión de tema: Se evaluaron en forma retrospectiva, entre mayo del 2009 y diciembre del 2011, 157 pacientes con patología suprarrenal. En total, eran 95 mujeres y 61 hombres, de 33 a 78 años (media: 55 años). El protocolo de estudio consistió en una tomografía computada (TC) sin contraste intravenoso (IV), con toma de la densidad de la lesión, seguida de una tomografía computada con contraste intravenoso y tiempo de lavado con toma de densidad de la lesión en tiempo portal y tardío a los 15 minutos (tiempo de lavado o wash-out). Las mediciones y cálculos realizados fueron: tamaño de la lesión suprarrenal, densidad media de la misma durante las tres fases estudiadas y porcentajes de lavado relativo y absoluto. Se realizó resonancia magnética (RM) y tomografía computada por emisión de positrones con 18F-fluorodesoxiglucosa (FDG-PET/TC) sólo en aquellos pacientes que así lo requirieron. Además, se compararon los resultados con los de la literatura actualizada sobre el tema. Hallazgos en imágenes: La conjunción de los datos clínicos, de laboratorio y las imágenes con el algoritmo propuesto permitió identificar 59 adenomas no funcionantes (49 unilaterales y 10 bilaterales), 29 adenomas funcionantes, 9 hiperplasias bilaterales, 4 mielolipomas (2 de ellos en una paciente con hiperplasia suprarrenal congénita virilizante simple), 2 quistes, 2 hematomas, 3 linfomas (2 secundarios y 1 primario bilateral), 30 metástasis, 5 carcinomas adrenocorticales, 12 feocromocitomas, 1 feocromocitoma maligno y 1 ganglioneuroma. Conclusión: La utilización de un algoritmo de estudio adecuado, con las herramientas diagnósticas más apropiadas y accesibles, permite la correcta caracterización de las lesiones suprarrenales. A su vez, evita la pérdida de tiempo, el diagnóstico incorrecto, la irradiación excesiva del paciente y la mala utilización de los recursos.(AU)

Objectives of training: The aim of this study is to propose an algorithm for the evaluation of adrenal lesions in order to arrive at the correct diagnosis in the shortest possible time. This method would favor the most appropriate therapeutic procedures for each pathology and may substantially modifi ed a given treatment. In spite of the fact that the structural features of lesions are generally non-specifi c, it is possible with imaging techniques, to establish compatible features which could help us differentiate benign from malignant lesions and with the contribution of the endocrinologist and the laboratory, to distinguish functional from non-functional ones. Topic revision: A retrospective evaluation was carried out from May 2009 to December 2011 on 157 patients with adrenal diseases, including 95 females and 61 males, from 33 to 78 years of age (mean age 55). The study protocol consisted of non-contrasted intravenous computed tomography, with lesion density measurement, followed by contrasted intravenous computed tomography and wash out time with lesion density determination in portal time and later at 15’ during wash out. Measurements and calculations were: adrenal lesion size, medium density and absolute and relative washing percentiles. Magnetic resonance and 18F-fl uorodesoxyglucose positron emission tomography was only performed on those patients who required these techniques. A comparison of the present results with those in the literature is included. Imaging fi ndings: Fifty-nine patients with non-functional adenoma were identifi ed (49 unilateral and 10 bilateral), 29 functional adenomas, 9 with bilateral hyperplasia, 4 myelolipomas (2 in a female patient with simple virilizing congenital adrenal hyperplasia), 2 cysts, 2 hematomas, 3 lymphomas (2 secondary and 1 primary bilateral), 30 metastases, 5 adrenocortical carcinomas, 12 pheochromocytomas,1 malignant pheochromocytoma, and 1 ganglioneuroma. Conclusion: The use of an appropriate study algorithm, with proper diagnostic tools, allows the correct characterization of adrenal lesions. Moreover, this approach prevents loss of time, a wrong diagnosis, excessive irradiation of the patient, and incorrect use of resources.(AU)

The multiple faces of CCL13 in immunity and inflammation.

CCL13/MCP-4, is a CC family chemokine that is chemoattractant for eosinophils, basophils, monocytes, macrophages, immature dendritic cells, and T cells, and its capable of inducing crucial immuno-modulatory responses through its effects on epithelial, muscular and endothelial cells. Similar to other CC chemokines, CCL13 binds to several chemokine receptors (CCR1, CCR2 and CCR3), allowing it to elicit different effects on its target cells. A number of studies have shown that CCL13 is involved in many chronic inflammatory diseases, in which it functions as a pivotal molecule involved in the selective recruitment of cell lineages to the inflamed tissues and their subsequent activation. Based on these studies, we suggest that blocking the actions of CCL13 can serve as a novel strategy for the generation of agents with anti-inflammatory activity. The main goal of this review is to present the current information about CCL13, its gene and protein structure and the roles of this chemokine during innate/adaptive immune responses in inflammatory diseases.

Experiencia en el tratamiento de quemaduras de cuero cabelludo / Scalp burns treatment experience

El cuero cabelludo es la barrera más externa y más importante del cráneo y del cerebro. Si bien las quemaduras de esta zona son raras, cuando se producen suelen estar causadas por alta tensión eléctrica, fuego, líquidos hirvientes u otras fuentes de calor. El objetivo de este trabajo es presentar una serie de casos de quemaduras de cuero cabelludo tratadas en los últimos10 años en el Hospital del Trabajador de Santiago (Chile).Se trata de un estudio descriptivo retrospectivo en el que se analizó la información demográfica y terapéutica de los pacientes que requirieron hospitalización al tiempo que se revisó la literatura al respecto. En total se registraron 2.266 consultas por quemaduras en la cabeza, de las cuales 34 fueron del cuero cabelludo y11 requirieron hospitalización; la mayoría fueron quemaduras eléctricas, 4 casos y por fuego, otros 4 casos. En el tratamiento, destacó el uso en 1 caso de colgajo libre asociado a colgajos locales de avance. En el tratamiento de las secuelas se utilizaron expansores y posteriormente colgajos locales de avance. Sólo una pequeña parte de los pacientes que consultan por quemaduras en la cabeza corresponden a quemaduras del cuero cabelludo. La mayoría son tratadas de forma ambulatoria y no requieren acciones mayores. Los pacientes con quemaduras eléctricas suelen requerir tratamientos más agresivos. Para el tratamiento de las secuelas son preferibles los expansores y los colgajos de avance (AU)

The scalp is the most external and important barrier of the skull and brain. Burns in this area are rare, but often caused by high voltage injuries, fire, liquid or other heat sources. The aim of this paper is to present a series of cases of scalp burns of the last 10 years in the Hospital del Trabajador de Santiago (Chile). This is a retrospective and descriptive study. We analyzed the demography and treatment of patients requiring hospitalization and we reviewed the literature. There were 2.266 visits for head burns, of which 34 patients consulted with scalp burns, 11 of them were hospitalized. Most were due to electrical burns, 4 patients, and fire,4 patients. In the treatment, highlighted the use in a case of free flap and local advancement flaps. In the management of sequelae, expanders and then local advancement flaps were performed. Only a small proportion of patients attending with head burns had scalp burns. Most were treated on as outpatient and did not require further action. The group of patients with electrical burns required more aggressive treatments while the management of the sequelaes is done with expanders and local advancement flaps (AU)

Fast modulation of alpha activity during visual processing and motor control.

Whereas some studies suggest that alpha rhythm promotes information processing in the human cortex (processing hypothesis), other studies suggest its involvement in an active cortical idling which prevents the interfering action of irrelevant information (idling hypothesis). In this study, this apparent contradiction was analyzed using a computing procedure which distinguishes phase-locked and non-phase-locked alpha response during the execution of a complex event-related visual-motor task. The electroencephalographies (EEGs) of 12 male volunteers were digitized (128 electrodes), band-pass filtered for isolating α wave, and event-related averaged during the execution of the visual-motor tasks. This procedure showed a phase-locked α response to stimuli and suppressed the non-phase-locked response. When EEG envelope of the α-wave was computed (Hilbert transformation) before the event-related average, the response of the alpha amplitude to stimuli was observed while the phase-locked α response vanished. Visual stimuli induced a short-lasting increase of phase-locked alpha activity and a long-lasting decrease of non-phase-locked alpha activity whose latency and amplitude changed with the cortical region (visual vs. parietal vs. frontal cortex), with the sensory-semantic information of visual stimuli, and with the tasks associated to them (comparing the alpha response to stimuli which were used for a visual-motor tasks with those passively observed). Alpha sub-bands around the individual alpha frequency peak showed a different phase-locked response. Finally, two early evoked potentials (C1-P1) showed a time latency similar to that computed for the phase-locked alpha response, suggesting that early evoked potentials are modified by the superposition of this alpha activity. Present data suggest that alpha activity promotes the cortical processing of information by increasing the phase-locked alpha activity and by decreasing the non-phase-locked alpha activity, and disturbs cortical processing under basal conditions when it is not phase-locked to any particular task.

[Severe acute ethylene glycol poisoning: diagnostic utility of osmolar gap monitoring]. / Intoxicación aguda grave por etilenglicol: valor de la monitorización del gap osmolar en su diagnóstico.

Ethylene glycol intake is a rare cause of alcohol poisoning in our practice setting. Most cases are voluntary, representing suicide attempts. Because delayed treatment leads to serious morbidity and high mortality (up to 50%), early diagnosis is essential for preventing harmful consequences and even death. Diagnosis is based on clinical suspicion and laboratory findings. Given that most hospitals do not have the means to measure the specific toxin in plasma, osmolar gap monitoring usually serves as a rapid diagnostic test for detecting the presence of osmotically active substances like ethylene glycol in plasma. We report a case of voluntary poisoning after the patient swallowed antifreeze. Successful treatment began early, with monitoring of the osmolar gap and plasma level correspondence. We also comment on the range of therapeutic options, emphasizing antidotes such as ethanol and fomepizole which provide the basis for treatment.

Intoxicación aguda grave por etilenglicol: valor de la monitorización del gap osmolar en su diagnóstico / Severe acute ethylene glycol poisoning: diagnostic utility of osmolar gap monitoring

La ingesta de etilenglicol (EG) es una causa poco frecuente de intoxicación alcohólica en nuestro medio. En la mayoría de los casos se trata de ingestas voluntarias con fines autolíticos. La demora en su tratamiento conlleva una elevada morbimortalidad (hasta del 50%), por ello el diagnóstico precoz es fundamental para evitar secuelas posteriores e incluso la muerte. El diagnóstico se basa en la sospecha clínica y la interpretación analítica. La mayoría de los centros carecen de la determinación específica del tóxico en el plasma. Así, clásicamente se utiliza la monitorización del gap osmolar como test diagnóstico rápido para detectar la presencia de sustancias osmóticamente activas en plasma, tal como el EG. Se presenta un caso de intoxicación voluntaria por anticongelante que fue atendida precozmente, con evolución clínica favorable, así como la monitorización del gap osmolar y su correlación con los niveles del tóxico en plasma. Se comentan también las distintas posibilidades terapéuticas, destacando los antídotos, base del tratamiento, como son el etanol y el fomepizol(AU)

Ethylene glycol intake is a rare cause of alcohol poisoning in our practice setting. Most cases are voluntary, representing suicide attempts. Because delayed treatment leads to serious morbidity and high mortality (up to 50%), early diagnosis is essential for preventing harmful consequences and even death. Diagnosis is based on clinical suspicion and laboratory findings. Given that most hospitals do not have the means to measure the specific toxin in plasma, osmolar gap monitoring usually serves as a rapid diagnostic test for detecting the presence of osmotically active substances like ethylene glycol in plasma. We report a case of voluntary poisoning after the patient swallowed antifreeze. Successful treatment began early, with monitoring of the osmolar gap and plasma level correspondence. We also comment on the range of therapeutic options, emphasizing antidotes such as ethanol and fomepizole which provide the basis for treatment(AU)

Quality of life improvement in Latin American patients suffering from chronic venous disorder using a combination of Ruscus aculeatus and hesperidin methyl-chalcone and ascorbic acid (quality study).

AIM: The present study assessed the effect of Ruscus aculeatus, hesperidin methyl-chalcone and ascorbic acid (HMC-AA), in the treatment of chronic venous disorders (CVD) in Latin American patients. METHODS: This study is an observational, single arm, multicentric and prospective trial. Patients suffering from CVD and belonging to C0s-C3 Clinical Etiological Anatomical and Physiopathological (CEAP) classes were included. Patient profiles, risk factors, clinical symptomatology and quality of life (QoL) assessed by SF-12 and CIVIQ questionnaires were evaluated at inclusion and after 12-week treatment. RESULTS: The main factors influencing the previous management of patients were age, gender, body mass index (BMI), familial history, physical activity, exposure to heat, heavy loads lifting, profession and clinical characteristics. All clinical symptoms significantly improved with treatment and, as BMI and CEAP classes increased. Ankle circumferences decreased over time, correlating with BMI and CEAP classes. The physical and psychological dimensions of the SF-12 score significantly increased over time and improved within each CEAP class. The CIVIQ score significantly improved over time, correlating with age and CEAP classes. CONCLUSION: A 12-week treatment with Ruscus aculeatus HMC-AA showed a significant decrease in the clinical symptoms and a significant improvement in the QoL of patients with CVD.

Proteolytic cleavage of chemokines by Trypanosoma cruzi's cruzipain inhibits chemokine functions by promoting the generation of antagonists.

Chagas disease is a chronic inflammatory disease caused by infection with Trypanosoma cruzi. Although it had a decline in recent years, it still affects millions of people in Latin America. The host immune response against this parasite is complex and relies on the development of an efficient T cell-mediated response; however, T. cruzi displays a number of evasion mechanisms allowing it to remain undetected even for years. One of these is the secretion of anti-inflammatory molecules such as proteases and the modulation of biological functions of chemokines. Our objective was to analyze the effect of a major cysteine protease, cruzipain, on a number of critical functions of several CC chemokines, both in vitro and in vivo. Initially, using a murine model of T. cruzi infection, we demonstrated that CCL-2 and CCL-12 chemokines are highly expressed at different stages and correlated with an increase in the expression of cruzipain. In addition, we demonstrated that cruzipain is capable of differentially cleaving CCL-2 and CCL-12 chemokines, as well as CCL-13. Analysis of the proteolysed products identified unique cleavage sites in these chemokines. These cruzipain-modified chemokine products were tested in chemotaxis assays using monocytic cells. We found that cruzipain treated-CCL-2 maintained its biological activity, in contrast to the closely related CCL-12 and CCL-13 chemokines, which showed little or null agonist activity after treatment. Furthermore, based on this analysis, a 14-mer cruzipain-derived chemokine peptide (CDCP-1) was chemically synthesized and tested for agonist activity using in vitro chemotaxis assays. Interestingly, CDCP-1 showed antagonist activity affecting in vitro migration of monocytic cells and calcium flux release. In conclusion, our results demonstrate that cruzipain modulates biological functions of chemokines through proteolytic cleavage, by generating chemokine-derived peptides with antagonist activities. This event could play a role during the latest phases of Chagas disease, when the parasite may differentially modulate chemokine-mediated inflammatory responses.

CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation.

Airway inflammation is characterized by selective recruitment of mononuclear and granulocytic cells. This recruitment is mediated by the action of chemotactic cytokines, such as chemokines. A number of chemokines and their receptors have been identified and proposed as potential therapeutic agents in allergic airway inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13), a CC chemokine that has been associated with allergic inflammatory diseases such as asthma and allergic rhinitis. To investigate alternative therapeutic agents to alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic peptides were designed and tested for their ability to modulate in vitro and in vivo chemokine-mediated functions. Our results show that one of these peptides, CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using monocytic cell lines. In addition, we found that CDIP-2 significantly reduced peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin-induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered as part of a novel group of anti-inflammatory agents based on chemokine-derived synthetic peptides.

[Nonagenarian's risk profile for living in a nursing home. The NonaSantfeliu study]. / Diferencias entre nonagenarios según su lugar de residencia. Estudio NonaSantfeliu.

OBJECTIVE: By means of a cross-sectional study, describe the differential characteristics between a group of inhabitants of a same municipality over 89 years of age who are permanently institutionalized and those of the same age who continue to live in the community, trying to identify a profile of nonagenarians with high risk of living in a nursing home. MATERIAL AND METHODS: One hundred and eighty six nonagenarians were studied: 137 (74%) were living in their home and 49 (26%) in a nursing home. Sociodemographic data, ability to perform basic daily activities with Barthel Index (BI) or instrumental activities with Lawton and Brody Index (LI), cognition with the Spanish version of the Mini-Mental State Examination (MEC) and comorbidity (Charlson Index) were evaluated. Cardiovascular risk factors and other prevalent diseases were also studied. RESULTS: A total of 143 women (76.5%) and 43 men with a mean age of 93.06 years were studied. A predominance of women, single persons, worse IL, and greater consumption of drugs was observed in the bivariate analysis in the nonagenarians living in residences and widowers than in those living in the community. The multivariate analysis showed that the features of being single and having a lower IL were independent factors of living in a nursing home. CONCLUSIONS: The main difference between nonagenargian patients who live in the community and those in residences is that the latter are mainly single and have a low score on a scale that quantities instrumental activities of the daily life.

Diferencias entre nonagenarios según su lugar de residencia. Estudio NonaSantfeliu / Nonagenarian's risk profile for living in a nursing home. The NonaSantfeliu study

Objetivo. Realizar un estudio transversal descriptivo de las características diferenciales entre un grupo de habitantes de un mismo municipio, mayores de 89 años y permanentemente institucionalizados, y los de la misma edad que siguen viviendo en la comunidad, para intentar identificar un perfil de nonagenario con alto riesgo de vivir en residencia. Material y métodos. Se evaluaron 186 nonagenarios, de los que 137 (74%) vivían en su domicilio mientras que 49 (26%), en residencia. Se recogieron los datos sociodemográficos, la capacidad para realizar actividades básicas se valoró con el índice de Barthel y para instrumentales con el índice Lawton y Brody (IL), la cognición con el miniexamen cognitivo de Lobo y la comorbilidad con el índice de Charlson. También se registró la existencia de enfermedades prevalentes, así como de algunos factores de riesgo cardiovascular. Resultados. Se trataba de 143 mujeres (76,5%) y 43 varones, con una edad media de 93,06 años. En el análisis bivariante se observa un predominio de mujeres, solteros, peor IL y un mayor consumo de fármacos en los nonagenarios de las residencias y de viudos en la comunidad. En el análisis multivariante se mantuvieron el ser soltero y el tener un menor IL como factores independientes de vivir en residencia. Conclusiones. La principal diferencia entre los pacientes nonagenarios que viven en la comunidad y los institucionalizados es que en estos últimos predomina el ser soltero y el tener una baja puntuación en una escala que cuantifica las actividades instrumentales de la vida diaria (AU)

Objective. By means of a cross-sectional study, describe the differential characteristics between a group of inhabitants of a same municipality over 89 years of age who are permanently institutionalized and those of the same age who continue to live in the community, trying to identify a profile of nonagenarians with high risk of living in a nursing home. Material and methods. One hundred and eighty six nonagenarians were studied: 137 (74%) were living in their home and 49 (26%) in a nursing home. Sociodemographic data, ability to perform basic daily activities with Barthel Index (BI) or instrumental activities with Lawton and Brody Index (LI), cognition with the Spanish version of the Mini-Mental State Examination (MEC) and comorbidity (Charlson Index) were evaluated. Cardiovascular risk factors and other prevalent diseases were also studied. Results. A total of 143 women (76.5%) and 43 men with a mean age of 93.06 years were studied. A predominance of women, single persons, worse IL, and greater consumption of drugs was observed in the bivariate analysis in the nonagenarians living in residences and widowers than in those living in the community. The multivariate analysis showed that the features of being single and having a lower IL were independent factors of living in a nursing home. Conclusions. The main difference between nonagenargian patients who live in the community and those in residences is that the latter are mainly single and have a low score on a scale that quantities instrumental activities of the daily life (AU)