44 research outputs found
Periodontal disease and diabetes : review of the literature
Aims: To provide updated knowledge on the relationship between periodontal disease and diabetes from an oral health perspective. Methods: A review of the English-language literature was performed, gathering articles on the two diseases published over the past 10 years. Results: Both diseases result from the confluence of various triggering and modifying factors, and there are inter-individual differences in the risk of their development. Recent research has shown that diabetes may increase the risk of periodontitis, and it has been proposed that chronic periodontal disease may influence the natural course of diabetes. There appears to be an association among oral infections, impaired sugar metabolism, and atherosclerosis, indicating a theoretical link between metabolic syndrome and periodontal disease. Clinical implications: Control of periodontal disease may enhance glycemic control in patients with type 2 diabetes. In turn, improved glycemic control may contribute to a better control of periodontal disease. © Medicina Oral S. L
Pancreas transplantation: differences in activity between Europe and the United States
Background. Although pancreas transplantation (PT) is the treatment of choice in selected diabetic patients, the International Pancreas Transplant Registry (IPTR) has reported important differences in activity between USA and Europe. Of all cases reported, 75% are from USA and only 23% from Europe. Therefore, an analysis of PT activity in selected European countries (SEC) and USA was performed
The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.
Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex
C-reactive protein for diagnosing late-onset infection in newborn infants
BACKGROUND: Late-onset infection is the most common serious complication associated with hospital care for newborn infants. Because confirming the diagnosis by microbiological culture typically takes 24 to 48 hours, the serum level of the inflammatory marker C-reactive protein (CRP) measured as part of the initial investigation is used as an adjunctive rapid test to guide management in infants with suspected late-onset infection. OBJECTIVES: To determine the diagnostic accuracy of serum CRP measurement in detecting late-onset infection in newborn infants. SEARCH METHODS: We searched electronic databases (MEDLINE, Embase, and Science Citation Index to September 2017), conference proceedings, previous reviews, and the reference lists of retrieved articles. SELECTION CRITERIA: We included cohort and cross-sectional studies evaluating the diagnostic accuracy of serum CRP levels for the detection of late-onset infection (occurring more than 72 hours after birth) in newborn infants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility for inclusion, evaluated the methodological quality of included studies, and extracted data to estimate diagnostic accuracy using hierarchical summary receiver operating characteristic (SROC) models. We assessed heterogeneity by examining variability of study estimates and overlap of the 95% confidence interval (CI) in forest plots of sensitivity and specificity. MAIN RESULTS: The search identified 20 studies (1615 infants). Most were small, single-centre, prospective cohort studies conducted in neonatal units in high- or middle-income countries since the late 1990s. Risk of bias in the included studies was generally low with independent assessment of index and reference tests. Most studies used a prespecified serum CRP threshold level as the definition of a 'positive' index test (typical cut-off level between 5 mg/L and 10 mg/L) and the culture of a pathogenic micro-organism from blood as the reference standard.At median specificity (0.74), sensitivity was 0.62 (95% CI 0.50 to 0.73). Heterogeneity was evident in the forest plots but it was not possible to conduct subgroup or meta-regression analyses by gestational ages, types of infection, or types of infecting micro-organism. Covariates for whether studies used a predefined threshold or not, and whether studies used a standard threshold of between 5 mg/L and 10 mg/L, were not statistically significant. AUTHORS' CONCLUSIONS: The serum CRP level at initial evaluation of an infant with suspected late-onset infection is unlikely to be considered sufficiently accurate to aid early diagnosis or select infants to undergo further investigation or treatment with antimicrobial therapy or other interventions
Master plan for the center of San JosÉ, Costa Rica: Challenges of the integrated approach and plan implementation
La regeneración de las ciudades existentes se enfrenta a importantes desafíos, dada la complejidad de actuar en entornos consolidados y habitados. La necesidad de aplicar un enfoque integrado y multidimensional, así como la dificultad de llevar a la práctica los planes que se diseñan, son algunos de los retos más importantes identificados en este ámbito. Este artículo analiza dichos retos a través del estudio del proceso de desarrollo del Plan Maestro de Regeneración Urbana y Reconversión Productiva de los Cuatro Distritos Centrales de San José, Costa Rica, con el objetivo de aportar claves para superar dichos retos. El centro urbano de San José, que en las últimas décadas ha sufrido un acusado proceso de despoblamiento y degradación, presenta importantes problemas, como la escasez de demanda residencial, un deficiente sistema de movilidad, deficientes infraestructuras de gestión del agua, alta vulnerabilidad frente al cambio climático, falta de integración del tejido urbano y un modelo productivo obsoleto. Desde la década de 1990, la Municipalidad de San José, en colaboración con otras instituciones, ha tratado de abordar dichos retos desarrollando planes y poniendo en marcha proyectos de actuación específicos. A pesar de los esfuerzos, los avances han sido escasos, principalmente por la ausencia de una visión común y una hoja de ruta para la regeneración urbana integral del centro. Como respuesta a esta problemática, y con apoyo del Banco Interamericano de Desarrollo, entre 2018 y 2019 se ha desarrollado el citado Plan Maestro. Este artículo expone los principales retos detectados durante el proceso de desarrollo de dicho Plan: el abordaje desde una perspectiva integrada de los desafíos de la regeneración urbana, y las barreras para una implementación efectiva de las propuestas. Para ello se identifican, en el primer caso, las problemáticas complejas existentes y las posibles sinergias en las actuaciones en las diferentes dimensiones urbanas; y en el segundo, las barreras a la coordinación interinstitucional y la falta de instrumentos de gestión y financiación adecuados, aportándose claves para superar dichas barreras
Mechanism of Action of Cytotoxic Macrolides Amphidinolide X and J.
4 páginas, 5 figuras, 1 tabla -- PAGS nros. 1027-1030Microtubules and actin filaments play important biological roles in mitosis, cytokinesis, cell signaling, intracellular transport, and cell motility of eukaryotic cells.1, 2 Molecules that target these cytoskeleton proteins are potential antitumor3 or anti-HIV agents.4 In fact, there are several clinical drugs that target the stabilization (paclitaxel-like behavior) or destabilization (vinca-like or colchicine-like behavior) of microtubules, specifically their heterodimeric component, α,β-tubulin.3 On the other hand, no actin-targeting drug has yet entered clinical studies.
Amphidinolides are a series of structurally dissimilar cytotoxic macrolides isolated from dinoflagellates (Amphidinium sp.).5–7 Their mechanisms of action are unknown, except that for one that has one of the largest rings, the 26-membered macrolide amphidinolide H (Amp-H, MW=562.73); this shows cytotoxicity in the nanomolar range against several carcinoma cell lines.8 Amp-H drastically and irreversibly deformed actin fibers;9 the actin fibers completely disappeared, and only a few disorganized aggregates remained in the cells. Amp-H induced multinucleated cells by disrupting actin organization (polyploid cells). In vitro assays on purified actin indicated that Amp-H stimulates actin polymerization, and stabilizes the actin filaments (F-actin).10, 11
In contrast, most of the smallest amphidinolides are cytotoxic in the micromolar range. For example, amphidinolide X (1, MW=448.59)12 and amphidinolide J (4, MW=390.56)13 have IC50 values of 1.3 and 6.9 μM, respectively, against the lymphocytic leukemia cell line L1210,12–14 although their mechanisms of action have not been reported. As these small amphidinolides are easier to synthesize than the larger molecules,15, 16 it would be desirable to identify their binding sites. Appropriate chemical modifications of these natural products might afford leads with activities below 0.1 μM that might eventually give rise to new antitumor agents. We report here biological studies of 1, the structurally related synthetic diolides 2 and 3, and 4 (Scheme 1). We examined their effect on the proliferation of A2780 (human ovarian carcinoma) and of LoVo (human colon carcinoma) cell lines, as well as on the cytoskeleton proteins tubulin, actin, and intermediate filaments in A549 (lung carcinoma) and PtK2 cells. Their effects on actin polymerization was then studied in vitroMICINN (Spanish Government) is acknowledged for grants BIO2010-16 351 (to J.F.D.), and CTQ 2009-13590 (to J.V.). M.B. thanks GlaxoSmithKline and the CNRS for a BDI grant. J.V. also thanks the Generalitat of Catalunya for a gift (2009SGR825). O.P. thanks the Fundació Cellex de Barcelona for a postdoctoral fellowship (May 2009–June 2010)Peer reviewe
Access to kidney transplantation in European adults aged 75-84 years and related outcomes: an analysis of the European Renal Association-European Dialysis and Transplant Association Registry
Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab.
There are an increasing number of treatments available for multiple sclerosis (MS). The early identification of optimal responders to individual treatments is important to achieve individualized therapy. With this aim, we performed a multicenter retrospective longitudinal study including 186 MS patients treated with natalizumab who were followed for 2 years. We analyzed the following variables at recruitment: sex, current age, age at disease onset, disease duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against human herpesvirus 6 (HHV-6) and the antibody response to Epstein-Barr virus (EBV) through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation to clinical response (no relapses or disability progression), and to NEDA-3 (no evidence of disease activity in terms of clinical response and no changes in MRI scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG titers and percentage change of HHV6 IgG titers between baseline and 6 month visits were significantly different in clinical responders and in NEDA-3 status (all of them remained significant in the multivariate analysis). We identified three variables for the early identification of natalizumab optimal responders in a rapid and cost-effective approach