Relationship between Apical Periodontitis and Metabolic Syndrome and Cardiovascular Events: A Cross-Sectional Study

Aim: Both apical periodontitis (AP) and metabolic syndrome (MetS) are associated with atherosclerotic cardiovascular disease (ACVD), the main cause of cardiovascular events. The aim of this study was to investigate the prevalence of AP and the oral inflammatory burden in control subjects and patients suffering cardiovascular events, analyzing the possible association between AP and the oral inflammatory burden with MetS. Materials and methods: Using a cross-sectional design, 83 patients suffering a cardiovascular event were recruited in the study group (SG), and 48 patients without cardiovascular events were included in the control group (CG). Periapical index (PAI) was used to diagnose AP, and total dental index (TDI) was used to assess the total oral inflammatory burden. Diagnosis of MetS was made by meeting three or more American Heart Association Scientific Statement components. Results: In the multivariate logistic regression analysis, the number of teeth with AP (OR = 2.3; 95% C.I. = 1.3-4.3; p = 0.006) and TDI scores (OR = 1.5; 95% C.I. = 1.2-1.9; p = 0.001), significantly correlated with cardiovascular events. MetS was strongly associated (OR = 18.0; 95% C.I. = 6.5-49.7; p = 0000) with cardiovascular events. Higher TDI scores were significantly associated with MetS (OR = 1.3; 95% C.I. = 1.1-1.6; p = 0.003. Neither the number of root-filled teeth (RFT) (OR = 0.9; 95% C.I. = 0.6-1.3; p = 0.61) nor the number of teeth with apical periodontitis (OR = 1.1; 95% C.I. = 0.8-1.7; p = 0.49) were associated with MetS. Conclusions: Apical periodontitis is significantly associated with cardiovascular events. Total oral inflammatory burden assessed by TDI, but not AP alone, is associated with MetS

1,3-diphenylpropan-1-ones as allosteric modulators of α7 nACh receptors with analgesic and antioxidant properties

Nicotine acethylcholine receptors (nAChRs) play critical roles in cognitive processes, neuroprotection and inflammation. Results: According to their substituents, 1,3-diphenylpropan-1-one derivatives act as α7 nAChRs negative allosteric modulators (NAM, OMe) or Type I positive allosteric modulators (PAMs, OH). Compounds 7 and 31 were the most effective (989 and 666% enhancement of ACh-induced currents) and potent (EC: 12.9 and 6.85 μM) PAMs. They exhibited strong radical scavenging values. Compound 31, selective over other neuronal nAChR subtypes and with acceptable pharmacokinetic profile, showed antinociceptive effects in a model of inflammatory pain. Conclusion: Compound 31 is a novel, potent and selective α7 nAChR PAM, displaying antioxidant and analgesic activities. The 1,3-diphenylpropan-1-one scaffold could be the base toward more advanced type I PAMs for the treatment of nAChR-mediated diseases.This work was supported by the Spanish MINECO: CSD2008-00005, The Spanish Ion Channel Initiative-CONSOLIDER INGENIO 2010, SAF2011-22802 and BFU2012-39092-C02. The Instituto de Neurociencias is a “Centre of Excellence Severo Ochoa”. We thank Susana Cámara Garrido for her assistance in the synthesis of some starting compounds and Susana Gerber for technical assistance. BBP thanks the CSIC for a predoctoral fellowship (JAE-Predoc from Junta para la Ampliación de Estudios, co-financed by FSE). Alpha7 nAChRPeer Reviewe

Péptidos bloqueantes de termoreceptores y sus usos

La invención se relaciona con péptidos helicoidales capaces de modular la activación de canales termosensoriales y con sus aplicaciones. Más concretamente, la invención se relaciona con péptidos con capacidad de bloquear la activación de los canales TRPV1 y TRPVA por parte de sus ligandos, con composiciones farmacéuticas que comprenden dichos péptidos y con el uso de dichos péptidos y dichas composiciones farmacéuticas para el tratamiento de dolor, inflamación, prurito, enfermedades de las vías respiratorias, enfermedades de la piel, mucosa y/o uñas y desórdenes asociados con desequilibrios del calcio.Peer reviewedUniversidad Miguel Hernández de Elche, Consejo Superior de Investigaciones CientíficasR Informe sobre el estado de la técnica publicado separadament

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Diseño de una tapicería textil para automoción

[ES] Desarrollo de una tapicería textil para automoción. Deberá analizarse la oferta actual existente en el mercado de automoción, valorándose del mismo aspectos técnicos y estéticos. Se definirán las posibilidades tecnológicas textiles que definirán el producto, seleccionándola entre las diferentes posibilidades. Es decir, se propondrán las materias adecuadas, así como las estructuras textiles y los procesos de acabado. Se realizará un análisis de la viabilidad del producto.Balsera Vizcaíno, B. (2015). Diseño de una tapicería textil para automoción. http://hdl.handle.net/10251/58306.TFG

Péptidos helicoidales y derivados de chalcona en la búsqueda de moduladores de canales iónicos

Ion channels are key elements of the plasmatic membranes. They are constituted as homo- or heteromeric protein complexes and selectively mediate the ion flux through the lipid bilayer to keep a gradient between both sides of the membrane. Cells make use of this gradient to regulate basic functions and, as a consequence, deregulation or abnormal functioning of ion channels are responsible for severe pathologies. Thus, and as a general approach, the modulation of such ion channels is crucial to treat several pathologies. Many of the explored strategies have been focused on the design of agonists and antagonists. However, alternative methodologies are required to overcome adverse effects associated to the classic design of substrate analogs. In this regard, the design of protein-protein interaction (PPI) and allosteric modulators are current powerful strategies.

Compounds with antioxidant activity and uses thereof

[ES] Compuestos con actividad antioxidante y sus usos. La invención se refiere a compuestos polifenólicos derivados de amida y urea y su uso como antioxidantes, además de composiciones farmacéuticas, cosméticas y alimentarias, entre otras, que los comprenden.[EN] The invention relates to polyphenol compounds derived from amide and urea and to the use thereof as antioxidants, as well as to pharmaceutical, cosmetic and food compositions, inter alia, comprising same.Peer reviewedCompuestos con actividad antioxidante y sus usosA1 Solicitud de patente con informe sobre el estado de la técnic

Compounds with antioxidant activity and uses thereof

[ES] Compuestos con actividad antioxidante y sus usos. La invención se refiere a compuestos polifenólicos derivados de amida y urea y su uso como antioxidantes, además de composiciones farmacéuticas, cosméticas y alimentarias, entre otras, que los comprenden.[EN] The invention relates to polyphenol compounds derived from amide and urea and to the use thereof as antioxidants, as well as to pharmaceutical, cosmetic and food compositions, inter alia, comprising same.Peer reviewedConsejo Superior de Investigaciones Científicas (España)B1 Patente sin examen previ

Compuestos con actividad antioxidante y sus usos

[EN] The invention relates to polyphenol compounds derived from amide and urea and to the use thereof as antioxidants, as well as to pharmaceutical, cosmetic and food compositions, inter alia, comprising same.[ES] Compuestos con actividad antioxidante y sus usos. La invención se refiere a compuestos polifenólicos derivados de amida y urea y su uso como antioxidantes, además de composiciones farmacéuticas, cosméticas y alimentarias, entre otras, que los comprenden.Peer reviewedConsejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic

Synthesis, high-throughput screening and pharmacological characterization of β-lactam derivatives as TRPM8 antagonists

The mammalian transient receptor potential melastatin channel 8 (TRPM8), highly expressed in trigeminal and dorsal root ganglia, mediates the cooling sensation and plays an important role in the cold hypersensitivity characteristic of some types of neuropathic pain, as well as in cancer. Consequently, the identification of selective and potent ligands for TRPM8 is of great interest. Here, a series of compounds, having a β-lactam central scaffold, were prepared to explore the pharmacophore requirements for TRPM8 modulation. Structure-activity studies indicate that the minimal requirements for potent β-lactam-based TRPM8 blockers are hydrophobic groups (benzyl preferentially or Bu) on R, R, R and R and a short N-alkyl chain (≤3 carbons). The best compounds in the focused library (41 and 45) showed IC values of 46 nM and 83 nM, respectively, in electrophysiology assays. These compounds selectively blocked all modalities of TRPM8 activation, i.e. menthol, voltage, and temperature. Molecular modelling studies using a homology model of TRPM8 identified two putative binding sites, involving networks of hydrophobic interactions, and suggesting a negative allosteric modulation through the stabilization of the closed state. Thus, these β-lactams provide a novel pharmacophore scaffold to evolve TRPM8 allosteric modulators to treat TRPM8 channel dysfunction.We thank the Ministry of Economy and Competitiveness (BES-2010-037112, BFU 2012-39092-C02, BFU2015- 70067-REDC, SAF2015-66275-C2-R), and the Generalitat Valenciana (PROMETEO II/2014/011) for financial support. We express our gratitude to Jessy Medina for technical assistancePeer Reviewe