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ÍtemSolo MetadatosATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure(2019) Delcour C.; Amazit L.; Patino L.C.; Magnin F.; Fagart J.; Delemer B.; Young J.; Laissue P.; Binart N.; Beau I.Purpose: Primary ovarian insufficiency (POI) is a frequent disorder that affects ~1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone (FSH), leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene variants, most cases remain idiopathic. The aim of the present study was to identify and validate functionally new sequence variants in ATG (autophagy-related genes) leading to POI. Methods: We have reanalyzed, in silico, the exome sequencing data from a previously reported work performed in 69 unrelated POI women. Functional experiments using a classical hallmark of autophagy, the microtubule-associated protein 1 light chain 3? (LC3), were then used to link these genes to this lysosomal degradation pathway. Results: We venture a functional link between ATG7 and ATG9A variants and POI. We demonstrated that variant ATG7 and ATG9A led to a decrease in autophagosome biosynthesis and consequently to an impairment of autophagy, a key biological process implicated in the preservation of the primordial follicles forming the ovarian reserve. Conclusion: Our results unveil that impaired autophagy is a novel pathophysiological mechanism involved in human POI. © 2018, American College of Medical Genetics and Genomics.- ÍtemSolo MetadatosDid Mozart Suffer from Gilles de la Tourette Syndrome?(2017) Palacios Sánchez, Leonardo; Botero Meneses, Juan Sebastián; Vergara-Méndez L.D.; Pachón N.; Martínez A.; Ramírez Clavijo, Sandra RocíoThe personal and private lives of great men and women in history, like writers, painters and musicians, have been the subject of great interest for many years. A clear example of this is the vast scrutiny is cast over the famous composer, Wolfgang Amadeus Mozart. What may have started as curiosity, rapidly evolved into extensive research, as the answers about the musician's legendary talent may lie in the details of his life (his childhood, his relationships, his quirks and his mannerisms). It is usually up to historians, anthropologists or philosophers to delve into the pages of old books, trying to grasp answers and clues. However, for some time, Physicians have sought their own part in solving the puzzle. The long told hypothesis regarding Mozart's diagnosis of Gilles de la Tourette syndrome will be examined. Could all of the peculiarities and oddities of the genius be caused by a neurological disorder? Or was this musical genius just an eccentric brilliant man?. © 2016 Asociación Colombiana de Psiquiatría
- ÍtemSolo MetadatosTemporal gene expression in the hippocampus and peripheral organs to endotoxin-induced systemic inflammatory response in caspase-1-deficient mice(2015) Mastronardi, Claudio Alberto; Paz-Filho, Gilberto; Zanoni, Martina; Molano González, Nicolás; Arcos-Burgos, Mauricio; Licinio, Julio; Wong, Ma-LiObjectives: Caspase-1 (casp1), a key protease involved in the systemic inflammatory response syndrome (SIRS), controls the brain expression of a set of eight genes: Nos2 and Ptgs2 (nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, two inducible enzymes), Cxcl1 and Cxcl10 (C-X-C motif chemokine ligand 1 and ligand 10), Tgtp and Gbp2 (T cell-specific GTPase 1 and guanylate-binding protein 2, two GTPases), Adamts1 (a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 1, a metalloprotease) and Il1rn (interleukin-1 receptor antagonist). Our objective was to ascertain whether casp1 also controlled the peripheral expression of these genes and, if so, to compare their central versus peripheral patterns of gene expression in immune and endocrine tissues during SIRS. Methods: Wild-type (wt) and casp1 knockout (casp1-/-) mice were injected with either saline or a high dose of endotoxin/lipopolysaccharide (LPS; 800 ?g/mice i.p.). Saline-injected mice were immediately euthanized after injection, whereas LPS-injected mice were sacrificed 6 and 12 h after LPS administration. Hippocampal, splenic and adrenal gene expressions were determined by real-time PCR. Results: Overall, casp1-/- mice showed a lower inflammatory response than wt mice. The expression levels of powerful proinflammatory factors such as Nos2 and Ptgs2 was reduced in casp1-/- mice. Moreover, a hierarchical clustering analysis aimed at studying patterns of gene coexpression revealed large alterations in the hippocampal pattern of casp1-/- mice. Surprisingly, the expression of Adamts1 was increased in the hippocampus and adrenals of casp1-/- mice. Conclusions: The resilience of casp1-/- mice to SIRS lethality is associated with a lower inflammatory response, loss of hippocampal gene coexpression patterns, and increased hippocampal Adamts1 gene expression. The latter might be beneficial for casp1-/- mice, since ADAMTS1 is likely to play a role in neuronal plasticity. The mechanisms described here may help the development of either novel biomarkers or therapeutic targets against SIRS/sepsis. © 2015 S. Karger AG, Basel.
- ÍtemSolo MetadatosHistidine-tryptophan-ketoglutarate solution versus blood cardioplegia in cardiac surgery: A propensity-score matched analysis(2018) Pizano, Alejandro; Montes, Felix Ramon; Carreño, Marisol; Echeverri, Dario; Umaña, Juan PabloBackground: Choosing a cardioplegic solution is a significant issue in modern cardiac surgery. Although different options are available, the optimal strategy for myocardial protection has not been established. The aim of this study was to compare intraoperative and postoperative effects of histidine–tryptophan–ketoglutarate (HTK) solution with those of standard blood cardioplegia with St Thomas No 2 solution. The study was conducted using a large cohort of adult patients undergoing complex cardiac surgery. Methods: This study was a single center retrospective review of prospectively collected data. Between January 2008 and December 2015, 4480 patients underwent cardiac surgery using cardiopulmonary bypass (CPB) and cardioplegic arrest. Patients were divided into a blood cardioplegia group (n = 3852) and an HTK solution group (n = 628). Propensity score matching was used to adjust for differences between the two groups, and 292 matched pairs were identified. The primary end point was Intensive Care Unit (ICU) length of stay (LOS). Secondary end points included intraoperative changes in serum sodium concentration, readmission to ICU, transfusion of blood products, 30-day hospital readmission, 30-day mortality, and the incidence of major postoperative complications. Results: No significant differences were found between the matched groups with regard to baseline characteristics. Aortic cross-clamp and CPB times were longer for the blood cardioplegia (147.4 versus 132.8 min; P less than .001). Administration of HTK solution was associated with acute and transient hyponatremia (141 versus 130 mmol/L; P less than .001). ICU LOS was comparable between the groups (5.4 versus 5.4 days; P = .585). No significant differences were noted in any other secondary end point. Conclusions: During complex cardiac surgery, both cardioplegia techniques were equivalent in terms of early clinical outcomes. © 2018 Forum Multimedia Publishing, LLC.
- ÍtemSolo MetadatosTemozolomide down-regulates P-glycoprotein in human blood-brain barrier cells by disrupting Wnt3 signaling(2014) Riganti, Chiara; Salaroglio, Iris C.; Pinzòn-Daza, Martha L.; Caldera, Valentina; Campia, Ivana; Kopecka, Joanna; Mellai, Marta; Annovazzi, Laura; Couraud, Pierre-Olivier; Bosia, Amalia; Ghigo, Dario; Schiffer, DavideLow delivery of many anticancer drugs across the blood-brain barrier (BBB) is a limitation to the success of chemotherapy in glioblastoma. This is because of the high levels of ATP-binding cassette transporters like P-glycoprotein (Pgp/ABCB1), which effluxes drugs back to the bloodstream. Temozolomide is one of the few agents able to cross the BBB; its effects on BBB cells permeability and Pgp activity are not known. We found that temozolomide, at therapeutic concentration, increased the transport of Pgp substrates across human brain microvascular endothelial cells and decreased the expression of Pgp. By methylating the promoter of Wnt3 gene, temozolomide lowers the endogenous synthesis of Wnt3 in BBB cells, disrupts the Wnt3/glycogen synthase kinase 3/?-catenin signaling, and reduces the binding of ?-catenin on the promoter of mdr1 gene, which encodes for Pgp. In co-culture models of BBB cells and human glioblastoma cells, pre-treatment with temozolomide increases the delivery, cytotoxicity, and antiproliferative effects of doxorubicin, vinblastine, and topotecan, three substrates of Pgp that are usually poorly delivered across BBB. Our work suggests that temozolomide increases the BBB permeability of drugs that are normally effluxed by Pgp back to the bloodstream. These findings may pave the way to new combinatorial chemotherapy schemes in glioblastoma. © 2013 Springer Basel.
- ÍtemSolo MetadatosExperimental intra-abdominal hypertension influences airway pressure limits for lung protective mechanical ventilation(2013) Cortes-Puentes, Gustavo A.; Cortes-Puentes, Luis A.; Adams, Alexander B.; Anderson, Christopher P.; Marini, John J.; Dries, David J.BACKGROUND: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) may complicate monitoring of pulmonary mechanics owing to their impact on the respiratory system. However, recommendations for mechanical ventilation of patients with IAH/ACS and the interpretation of thoracoabdominal interactions remain unclear. Our study aimed to characterize the influence of elevated intra-abdominal pressure (IAP) and positive end-expiratory pressure (PEEP) on airway plateau pressure (PPLAT) and bladder pressure (PBLAD). METHODS: Nine deeply anesthetized swineweremechanically ventilated via tracheostomy: volume-controlled mode at tidal volume (VT) of 10mL/kg, frequency of 15, inspiratory-expiratory ratio of 1:2, and PEEP of 1 and 10 cm H2O (PEEP1 and PEEP10, respectively). A tracheostomy tube was placed in the peritoneal cavity, and IAP levels of 5, 10, 15, 20, and 25 mm Hg were applied, using a continuous positive airway pressure system. At each IAP level, PBLAD and airway pressure measurements were performed during both PEEP1 and PEEP10. RESULTS: PBLAD increased as experimental IAP rose (y = 0.83x + 0.5; R2 = 0.98; p G 0.001 at PEEP1). Minimal underestimation of IAP by PBLAD was observed (j2.5 T 0.8 mm Hg at an IAP of 10-25 mm Hg). Applying PEEP10 did not significantly affect the correlation between experimental IAP and PBLAD. Approximately 50% of the PBLAD (in cm H2O) was reflected by changes in P PLAT, regardless of the PEEP level applied. Increasing IAP did not influence hemodynamics at any level of IAP generated. CONCLUSION: With minimal underestimation, PBLAD measurements closely correlated with experimentally regulated IAP, independent of the PEEP level applied. For each PEEP level applied, a constant proportion (approximately 50%) of measured PBLAD (in cm H2O) was reflected in PPLAT. A higher safety threshold for PPLAT should be considered in the setting of IAH/ACS as the clinician considers changes in VT. A strategy of reducing V T to cap PPLAT at widely recommended values may not be warranted in the setting of increased IAP. Copyright © 2013 Lippincott Williams and amp; Wilkins.
- ÍtemSolo MetadatosPrevalence of delayed neurodevelopment in children from Bogotá, Colombia, South America(2007) Vélez van Meerbeke, Alberto Francisco; Talero Gutiérrez, Claudia; González Reyes, Rodrigo EstebanBackground: Undiagnosed children with neurodevelopment delay disorders (NDD) frequently experience school difficulties, leading to school desertion or academic failure with subsequent familial, social and work-related problems. Methods: In 2004-2005, we conducted a cross-sectional study to determine the prevalence of developmental delay among preschoolers in Bogotá (Colombia); convenience samples in several socioeconomic areas of the city were screened to define the prevalence of NDD. Parents and teachers were interviewed to identify children with possible NDD. Selected children were evaluated with a neurodevelopmental abbreviated scale (EAD-1). Results: We screened 2,043 preschool children aged less than 60 months; 288 suspected cases were examined individually using the EAD-1 scale. One or more abnormal items (alert category) were found in 67 (23.3%) children, for an estimated prevalence of 32.8‰ children less than 5 years of age, including deficits in gross motor function (9.3‰), personal-social interactions (9.8‰), fine motor skills (10.3‰), auditory language delay (18.6‰) and overall delay (10.8‰). Conclusions: There is limited information regarding the prevalence of neurodevelopmental delay in nonindustrialized countries. The prevalence obtained in Bogotá, Colombia, is within the expected range; however, we identified NDD among apparently healthy children from nurseries and kindergartens, who had previously been undiagnosed and untreated. Lack of evaluation of developmental milestones in children in Colombia is a substantial public health problem that will require effective intervention. Copyright © 2007 S. Karger AG.
- ÍtemSolo MetadatosSarconesiopsis magellanica (Diptera: Calliphoridae) excretions and secretions have potent antibacterial activity(2014) Díaz-Roa, Andrea; Gaona, María A.; Segura, Nydia A.; Suárez, Diana; Patarroyo, Manuel A.; Bello, Felio J.The most important mechanism for combating infection using larval therapy depends on larval excretions and secretions (ES). The present work was aimed at evaluating Sarconesiopsis magellanica (Diptera: Calliphoridae) ES antibacterial activity in six bacterial strains (three Gram-positive and three Gram-negative) and comparing this to the effect of Lucilia sericata-derived ES. Antibacterial activity at 50. ?g/mL minimum inhibitory concentration (MIC) was observed for Staphylococcus epidermidis ATCC-12228 and Staphylococcus aureus ATCC-29213 strains, when the turbidimetry test involving S. magellanica ES was used; the rest of the bacterial strains (Staphylococcus aureus ATCC-6538, Pseudomonas aeruginosa ATCC-10145, Pseudomonas aeruginosa ATCC-9027 and Pseudomonas aeruginosa ATCC-27853) were inhibited at a 100. ?g/mL MIC. Twice the amount was required to inhibit the aforementioned bacteria with L. sericata-derived ES using this same technique; a similar trend was observed when the agar diffusion method was used instead. Furthermore, when the previously established MIC for each bacterial strain was used, their colonies became reduced following 1-6. h incubation with S. magellanica derived ES, whilst the reduction occurred from 2 to 6. hours with those from L. sericata. Although the MIC for each strain obtained with ciprofloxacin was lower than those established when using either blowfly derived-ES, the gradual reduction of the colonies occurred at a longer incubation time (6. h or more). The results showed that S. magellanica ES antibacterial activity was more potent and effective, compared to that of L. sericata-derived ES. © 2014 Elsevier B.V.
- ÍtemSolo MetadatosEndophthalmitis after pars plana vitrectomy: Results of the pan American collaborative retina study group(2011) Wu L.; Berrocal M.H.; Arévalo J.F.; Carpentier C.; Rodriguez F.J.; Alezzandrini A.; Farah M.E.; Roca J.A.; Maia M.; Saravia M.; Morales-Cantón V.; Graue-Wiechers F.; Cardillo J.A.Purpose: To determine the incidence of endophthalmitis after 20-, 23-, and 25-gauge pars plana vitrectomies (PPVs). Methods: Retrospective comparative case series of consecutive patients who underwent 20-, 23-, or 25-gauge PPV at 11 centers from Latin America between 2005 to 2009. Pars plana vitrectomy cases were identified through a search of the billing records of each institution. Cases of PPV performed in the management of trauma, endophthalmitis, and combined PPV phacoemulsification cases were excluded. Endophthalmitis was diagnosed by clinical criteria regardless of the microbiologic results. The incidence of post-PPV endophthalmitis was compared between 20-, 23-, and 25-gauge PPVs. Results: A total of 35,427 cases of PPV were identified during the study period (n = 19,865 for 20 gauge, n = 10,845 for 23 gauge, and n = 4,717 for 25 gauge). The 5-year post-PPV endophthalmitis incidence rates were 0.020% (4 of 19,865), 0.028% (3 of 10,845), and 0.021% (1 of 4,717) for 20 gauge, 23 gauge, and 25 gauge, respectively (P = 0.9685). Conclusion: Small-gauge transconjunctival PPV does not appear to increase the rates of post-PPV endophthalmitis. © The Ophthalmic Communications Society, Inc.
- ÍtemSolo MetadatosComparison of spinal anesthesia with combined sciatic-femoral nerve block for outpatient knee arthroscopy(2008) Montes, Felix R.; Zarate, Eduardo; Grueso, Reinaldo; Giraldo, Juan C.; Venegas, Maria P.; Gomez, Andrea; Rincón, Jose D.; Hernadez, Marcela; Cabrera, MarianaStudy Objective: To compare spinal anesthesia and combined sciatic-femoral nerve block for outpatient knee arthroscopy. Design: Prospective, randomized, controlled study. Setting: Postoperative recovery area at a university-affiliated medical center. Patients: 50 ASA physical status I and II adult outpatients undergoing arthroscopic knee surgery. Interventions: Study subjects were equally divided (n = 25 each) into spinal and sciatic-femoral groups. Spinal group patients received spinal anesthesia with 7.5 mg of 0.5% hyperbaric bupivacaine. Sciatic-femoral group patients received combined sciatic-femoral nerve blocks using a mixture of 20 mL of lidocaine 2% plus 20 mL of bupivacaine 0.5%. Measurements: Times including that from arrival in the operating room to readiness for surgery, duration of surgery, recovery time, and patient satisfaction were recorded. Analgesia and occurrence of adverse events also were recorded. Main Results: No significant differences between the two groups were found for any of the study measurements of recovery. After discharge, postoperative pain differed significantly between groups only at 6 hours (P less than 0.002). Patient satisfaction was high with both techniques. Conclusions: Combined sciatic-femoral nerve block for outpatient arthroscopic knee surgery offers satisfactory anesthesia, with a clinical profile similar to that of low-dose spinal anesthesia. Sciatic-femoral nerve blocks are associated with significantly lower pain scores during the first 6 postoperative hours. © 2008 Elsevier Inc. All rights reserved.
