Cardiopulmonary phenotype in systemic sclerosis associated pulmonary hypertension.

INTRODUCTION: Pulmonary hypertension (PH) associated with systemic sclerosis (SSc) increases morbidity and mortality. Cardiopulmonary comorbidities, as per the 2021 PH consensus, play a role in the choice of therapy between monotherapy and combination therapy. METHODS: A cross-sectional study was conducted in patients with SSc based on the 2013 ACR/EULAR criteria or very early disease (VEDOSS 2011). PH was considered if they met the following criteria: pulmonary artery systolic pressure (PASP)>39mmHg or peak tricuspid regurgitation velocity (PTRV)>3.4m/s, PASP between 33 and 39mmHg or PTRV between 2.9 and 3.4m/s plus two additional findings suggestive of PH. PH was classified as type 2 if LVEF<50% or moderate to severe diastolic dysfunction was present; type 3 if extensive interstitial disease on tomography>20% or forced vital capacity (FVC)<75%; type 4 if abnormalities related to embolism were detected on scintigraphy or tomography. If patients did not meet these criteria, they were classified as type 1 PH. Complete data on cardiopulmonary risk factors and other factors were required. The frequency of these factors in the population and differences between groups based on risk factors were estimated. RESULTS: A total of 228 patients were selected. Three had type 2 PH, 24 had type 3, and 40 had type 1 PH, with the majority (75%) having at least one cardiopulmonary risk factor, and 47.5% having more than one. Mild diastolic dysfunction (25%) and hypertension (35%) were the most prevalent. In the type 1 PH group, those with risk factors experienced an increase in the number of years with Raynaud's phenomenon, anticentromere antibodies, and gastrointestinal symptoms (p<0.05). CONCLUSION: In patients with PH, 75% have one, and 45% have two or more risk factors.

Feedback regulation by Atf3 in the endothelin-1-responsive transcriptome of cardiomyocytes: Egr1 is a principal Atf3 target.

Endothelin-1 promotes cardiomyocyte hypertrophy by inducing changes in gene expression. Immediate early genes including Atf3 (activating transcription factor 3), Egr1 (early growth response 1) and Ptgs2 (prostaglandin-endoperoxide synthase 2) are rapidly and transiently up-regulated by endothelin-1 in cardiomyocytes. Atf3 regulates the expression of downstream genes and is implicated in negative feedback regulation of other immediate early genes. To identify Atf3-regulated genes, we knocked down Atf3 expression in cardiomyocytes exposed to endothelin-1 and used microarrays to interrogate the transcriptomic effects. The expression of 23 mRNAs (including Egr1 and Ptgs2) was enhanced and the expression of 25 mRNAs was inhibited by Atf3 knockdown. Using quantitative PCR, we determined that knockdown of Atf3 had little effect on up-regulation of Egr1 mRNA over 30 min, but abolished the subsequent decline, causing sustained Egr1 mRNA expression and enhanced protein expression. This resulted from direct binding of Atf3 to the Egr1 promoter. Mathematical modelling established that Atf3 can suffice to suppress Egr1 expression. Given the widespread co-regulation of Atf3 with Egr1, we suggest that the Atf3-Egr1 negative feedback loop is of general significance. Loss of Atf3 caused abnormal cardiomyocyte growth, presumably resulting from the dysregulation of target genes. The results of the present study therefore identify Atf3 as a nexus in cardiomyocyte hypertrophy required to facilitate the full and proper growth response.

A novel non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3).

The canonical pathway of regulation of the GCK (germinal centre kinase) III subgroup member, MST3 (mammalian Sterile20-related kinase 3), involves a caspase-mediated cleavage between N-terminal catalytic and C-terminal regulatory domains with possible concurrent autophosphorylation of the activation loop MST3(Thr(178)), induction of serine/threonine protein kinase activity and nuclear localization. We identified an alternative 'non-canonical' pathway of MST3 activation (regulated primarily through dephosphorylation) which may also be applicable to other GCKIII (and GCKVI) subgroup members. In the basal state, inactive MST3 co-immunoprecipitated with the Golgi protein GOLGA2/gm130 (golgin A2/Golgi matrix protein 130). Activation of MST3 by calyculin A (a protein serine/threonine phosphatase 1/2A inhibitor) stimulated (auto)phosphorylation of MST3(Thr(178)) in the catalytic domain with essentially simultaneous cis-autophosphorylation of MST3(Thr(328)) in the regulatory domain, an event also requiring the MST3(341-376) sequence which acts as a putative docking domain. MST3(Thr(178)) phosphorylation increased MST3 kinase activity, but this activity was independent of MST3(Thr(328)) phosphorylation. Interestingly, MST3(Thr(328)) lies immediately C-terminal to a STRAD (Sterile20-related adaptor) pseudokinase-like site identified recently as being involved in binding of GCKIII/GCKVI members to MO25 scaffolding proteins. MST3(Thr(178)/Thr(328)) phosphorylation was concurrent with dissociation of MST3 from GOLGA2/gm130 and association of MST3 with MO25, and MST3(Thr(328)) phosphorylation was necessary for formation of the activated MST3-MO25 holocomplex.

Mutation spectrum in South American Lynch syndrome families.

BACKGROUND: Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system. METHODS: We compiled data from publications and hereditary cancer registries to characterize the Lynch syndrome mutation spectrum in South America. In total, data from 267 families that fulfilled the Amsterdam criteria and/or the Bethesda guidelines from Argentina, Brazil, Chile, Colombia and Uruguay were included. RESULTS: Disease-predisposing mutations were identified in 37% of the families and affected MLH1 in 60% and MSH2 in 40%. Half of the mutations have not previously been reported and potential founder effects were identified in Brazil and in Colombia. CONCLUSION: The South American Lynch syndrome mutation spectrum includes multiple new mutations, identifies potential founder effects and is useful for future development of genetic testing in this continent.

Glycogen synthase kinases 3alpha and 3beta in cardiac myocytes: regulation and consequences of their inhibition.

Inhibition of glycogen synthase kinase 3beta (GSK3beta) as a consequence of its phosphorylation by protein kinase B/Akt (PKB/Akt) has been implicated in cardiac myocyte hypertrophy in response to endothelin-1 or phenylephrine. We examined the regulation of GSK3alpha (which we show to constitute a significant proportion of the myocyte GSK3 pool) and GSK3beta in cardiac myocytes. Although endothelin increases phosphorylation of GSK3 and decreases its activity, the response is less than that induced by insulin (which does not promote cardiac myocyte hypertrophy). GSK3 phosphorylation induced by endothelin requires signalling through the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade and not the PKB/Akt pathway, whereas the reverse is true for insulin. Cardiac myocyte hypertrophy involves changes in morphology, and in gene and protein expression. The potent GSK3 inhibitor 1-azakenpaullone increases myocyte area as a consequence of increased cell length whereas phenylephrine increases both length and width. Azakenpaullone or insulin promotes AP1 transcription factor binding to an AP1 consensus oligonucleotide, but this was significantly less than that induced by endothelin and derived principally from increased binding of JunB protein, the expression of which was increased. Azakenpaullone promotes significant changes in gene expression (assessed by Affymetrix microarrays), but the overall response is less than with endothelin and there is little overlap between the genes identified. Thus, although GSK3 may contribute to cardiac myocyte hypertrophy in some respects (and presumably plays an important role in myocyte metabolism), it does not appear to contribute as significantly to the response induced by endothelin as has been maintained.

Transthoracic Echocardiographic Examination in the Rabbit Model.

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to that of humans and that of other large animal models such as dogs and pigs. However, the rabbit model has the additional advantage of lower maintenance costs compared to other large animal models. The longitudinal evaluation of cardiac function using echocardiography, when appropriately implemented, is a useful methodology for preclinical assessment of novel therapies for heart failure with reduced ejection fraction (e.g. cardiac regeneration). The correct use of this non-invasive tool requires the implementation of a standardized examination protocol following international guidelines. Here we describe, step by step, a detailed protocol supervised by veterinary cardiologists for performing echocardiography in the rabbit model, and demonstrate how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Percutaneous Contrast Echocardiography-guided Intramyocardial Injection and Cell Delivery in a Large Preclinical Model.

Cell and gene therapy are exciting and promising strategies for the purpose of cardiac regeneration in the setting of heart failure with reduced ejection fraction (HFrEF). Before they can be considered for use, and implemented in humans, extensive preclinical studies are required in large animal models to evaluate the safety, efficacy, and fate of the injectate (e.g., stem cells) once delivered into the myocardium. Small rodent models offer advantages (e.g., cost effectiveness, amenability for genetic manipulation); however, given inherent limitations of these models, the findings in these rarely translate into the clinic. Conversely, large animal models such as rabbits, have advantages (e.g., similar cardiac electrophysiology compared to humans and other large animals), whilst retaining a good cost-effective balance. Here, we demonstrate how to perform a percutaneous contrast echocardiography-guided intramyocardial injection (IMI) technique, which is minimally invasive, safe, well tolerated, and very effective in the targeted delivery of injectates, including cells, into several locations within the myocardium of a rabbit model. For the implementation of this technique, we also have taken advantage of a widely available clinical echocardiography system. After putting in practice the protocol described here, a researcher with basic ultrasound knowledge will become competent in the performance of this versatile and minimally invasive technique for routine use in experiments, aimed at hypothesis testing of the capabilities of cardiac regenerative therapeutics in the rabbit model. Once competency is achieved, the whole procedure can be performed within 25 min after anaesthetizing the rabbit.

[Basic standards for Colombian paternity testing laboratories, 2005]. / Estándares baisicos para los laboratorios de pruebas de paternidad en Colombia, 2005.

The Commission for Accreditation and Surveillance of Laboratories Practicing DNA Paternity Tests (created by the Colombian Law 721/2001) set up sub-commission to review the current basic Colombian standards required for paternity testing laboratories and make specific recommendations re the pertinent technical aspects in Colombia, taking ISO 17025 as current reference. This document contains such recommendations for Colombia.

[Detection of transgenic proteins in maize flour marketed in Bogotá, Colombia]. / Detección de proteínas transgénicas en harinas de maíz comercializadas en Bogotá, Colombia.

Objective To detect the presence or absence of transgenic proteins derived from GM crops in maize flour marketed in Bogota D.C., Colombia. Methods 11 extraction protocols for total protein were evaluated in 17 precooked flour, two uncooked and three positive controls. Subsequently, the presence of 7 transgenic proteins (CP4-EPSPS, Cry1Ab, Cry1Ac, Cry1F, Cry2A, Cry34Ab1 and Cry3Bb1) using commercial ELISA kits was determined. Results It was determined that the best protocol for total protein extraction was buffer with Triton X-100, which allowed obtaining protein concentrations greater than 0.5 mg per gram of flour and does not generate interference with the ELISA technique. Four transgenic proteins were detected: CP4EPSPS, Cry1F, Cry1Ab and Cry34Ab1 in precooked and uncooked flour with percentages varying between 20 and 100 %. Conclusion Seven of the 19 maize flours contain traces of transgenic protein (B2,B8,A3,O3,O1,C1 and C2) that provide resistance to lepidopterans and coleopterans, and tolerance to glyphosate herbicide, (CP4EPSPS- Cry1Ab, Cry1F, Cry34Ab1 and Cry3Bb1). All detected events are approved for human consumption in Colombia, according to the Ministry of Health and Social Protection.

MLH1 and MSH2 mutations in Colombian families with hereditary nonpolyposis colorectal cancer (Lynch syndrome)--description of four novel mutations.

This study searched for mutations in the MLH1 and MSH2 genes in 23 unrelated Colombian families with suspected hereditary nonpolyposis colorectal cancer (HNPCC). The families were grouped according to the fulfillment of the Amsterdam II criteria or the Bethesda guidelines. We screened all probands by single-strand conformational polymorphism (SSCP) and direct DNA sequencing. Eleven families fulfilled the Amsterdam criteria II and 12 families the Bethesda guidelines. Germline mutations were detected in 11 families, which corresponds to a mutation detection rate of 48%. When only families fulfilling the Amsterdam II criteria were analyzed, the mutation detection rate rose to 82%. Only 8% of the mutation detection rate was found in families following the Bethesda guidelines. Three mutations were shared by two different families, which corresponds to a total of eight different mutations, seven of them found in the MLH1 gene and one in the MSH2 gene. We have identified four mutations that have not been previously reported to the International Collaborative Group of HNPCC. Three of these are pathogenic, a single base substitution (C > T) at codon 640, exon 17, a G deletion at codon 619, exon 16 and in the MLH1 gene and a two-nucleotide deletion (TG) at codon 184, exon 3 in the MSH2. Also, an unclassified variant, a substitution (C > G) at the codon 141, exon 5 of the MLH1, was detected.

[Identification of point mutations in the 21-hydroxylase gene in patients affected with congenital adrenal hyperplasia]. / Identificación de mutaciones puntuales del gen de la 21-hidroxilasa en pacientes afectados con hiperplasia suprarrenal congénita.

INTRODUCTION: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder due to impaired cortisol secretion. Approximately 95% of CAH cases are caused by defects in the 21-hydrodylase2 (CYPA2) gene. The spectrum of clinical manifestations includes a severe and mild form of expression. The frequency of the following point mutations was determined: P30L, IVS2-12A/C-G splice, Del 8pb, I172N, cluster Ex6, V281L, Q318X, R356W and P453S. MATERIALS AND METHODS: The 58 patients consisted of 48 with the severe form of CAH and 10 with the mild form. Point mutations in the hydroxylase gene were isolated by allele-specific PCR and PCR-ACRS (amplification created restriction site), and their frequency was determined. RESULTS: Alternate alleles were identified in 82.8% of the samples. The most frequent mutations were IVS2-12A/C-G splice (26.7%), Q318X (21.5%), V281L (12.1%) and I172N (12.1%). DISCUSSION: The most frequent mutations were similar to those observed in other countries, except for Q318X. Although its frequency was higher but similar to that observed in Latin American countries, it contrasted with those of other continents and indicated the possible influence of genetic background in its expression. Several of the mutations were associated with specific clinical forms related to the enzyme activity. In the milder forms of CAH, several alleles were detected. These were important because these patients can have children with the virilizing and salt wasting forms. Recognition of the allelic forms of CAH will permit more specific genetic counseling and prenatal diagnosis.

[Detection mutations in the DNA mismatch repair genes of hMLH1 and hMSH2 genes in Colombian families with suspicion of hereditary non-polyposis colorectal carcinoma (Lynch syndrome)]. / Detección de mutaciones de los genes hMLH1 y hMSH2 del sistema de reparación de malos apareamientos del ADN en familias colombianas sospechosas de cancer colorrectal no polipósico hereditario (síndrome de Lynch).

INTRODUCTION: Colorectal cancer (CRC) is the second highest cause of cancer mortality in developed countries. In Colombia, CRC ranks fifth as a cause of cancer death. Approximately 75% of CRC appear to be spontaneous and 25% are familial, with 5% of the latter clearly hereditary. Of these, hereditary non-polyposis colorectal carcinoma (HNPCC)-or Lynch syndrome is the most important. OBJECTIVE: Herein, the two most important genes involved in Lynch syndrome, the hMLH1 and hMSH2 were analyzed for presence of mutations. MATERIALS AND METHODS: Seventeen Colombian families that fulfilled the Amsterdam II criteria or Bethesda guidelines for Lynch syndrome were selected. The of 35 exons of hMLH1 and hMSH2 genes were screened by SSCP and those with electrophoretic variants were sequenced. RESULTS: Eight germinal mutations were detected, corresponding to a 47% detection mutation rate. Six of the eight mutations have previously been reported. These consisted of the following mutations: a single base substitution at the donor splicing site of exon 9, a single base substitution (A>G) at codon 755 of the exon 17, and another single base substitution (G>A) at codon 681 of exon 18. The two novel mutations consisted of a single base substitution (C>T) at codon 640 of exon 17 of the hMLH1 gene and a two-nucleotide deletion (TG) at codon 184 of exon 3 of hMSH2 gene. In addition, two families were observed with a polymorphism in the intron 13 (G>A) nt 1558+14, of hMLH1 gene. CONCLUSIONS: This study represented the first survey for detecting mutations associated with Lynch syndrome in Colombia, and is intended to lead to the establishment of a management and prevention program.

Estado de la investigación científica y el acceso a los recursos genéticos por grupos de investigación colombianos / Status of scientific research and the Access to genetic resources by Colombian research groups

RESUMEN Colombia participa actualmente con el 14% de la biodiversidad del planeta, que se considera uno de los activos más importantes del país. En todo el mundo ocupa el primer lugar en diversidad de especies de aves y el segundo en plantas, de ahí la importancia de controlar el acceso a las especies nativas. Por lo tanto, el objetivo del estudio fue analizar el estado actual de la investigación científica y el acceso a los recursos genéticos por parte de los grupos de investigación colombianos a través de la revisión de sus proyectos de investigación descritos en la base de datos nacional de Minciencias GrupLAC para el período 2013-2018. Los grupos de investigación se clasificaron en seis áreas según el programa nacional de ciencia y tecnología (Biotecnología, Ciencias Básicas, Ciencias del Mar, Salud, Ciencias Agrícolas y Biodiversidad y Hábitat) y los proyectos de investigación se dividieron según en las actividades exceptuadas de solicitar contrato de acceso y las que lo requieren, según las modificaciones a la legislación colombiana entre 2013 y 2017. Los resultados muestran que del total de 2168 proyectos revisados, (que incluyen modalidades exceptuadas de solicitar contrato de acceso como los que lo requieren) 198 (9,1%) emplearon especies nativas en sus investigaciones divididas en las siguientes categorías: sistemática molecular (38,3%), ecología molecular (18,1%), biogeografía (2,7 %), y otros (40, 9%). El Ministerio del medio ambiente reporto un total de 273 solicitudes de contratos de Acceso a Recurso Genéticos para el mismo periodo. Los últimos desarrollos legislativos en Colombia, diferencian y simplifican el procedimiento para realizar investigaciones sobre recursos genéticos, han tenido un impacto positivo, dado que el número de solicitudes de contratos de acceso a recursos genéticos se incrementó en los últimos 5 años.

ABSTRACT Colombia currently participates with 14% of the planet's biodiversity, which is considered one of the most important assets in the country. Around the world it occupies the first place in diversity of bird species and second in plants, hence the importance of controlling access to native species. Therefore, the objective of the study was to analyze the current state of scientific research and access to genetic resources by Colombian research groups through the review of their research projects described in the national database of Minciencias GrupLAC for the 2013-2018 period. The research groups were classified into six areas according to the national science and technology program (Biotechnology, Basic Sciences, Marine Sciences, Health, Agricultural Sciences and Biodiversity and Habitat); and the research projects were divided according to the activities excepted from requesting an access contract and those that require it, according to the modifications to Colombian legislation between 2013 and 2017. The results show that of the total of 2168 projects reviewed, 198 (9, 1%) used native species in their research divided into the following categories: molecular systematics (38.3%), molecular ecology (18.1%), biogeography (2.7%), and others (40, 9%). For its part, the Ministry of the environment reported a total of 273 applications for Genetic Resource Access contracts for the same period. It is clear that the latest legislative developments in Colombia, differentiate and simplify the procedure for conducting research on genetic resources, have had a positive impact, given that the number of requests for contracts for access to genetic resources has increased in the last 5 years.

An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy.

Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality.

Allele frequencies for 13 STR's from two Colombian populations: Bogotá and Boyacá.

We present information from populations living in Bogotá and Boyacá, for nine short tandem repeats (STR's) already studied and four new alleles not reported in previous Colombian populations.

[Frequency of congenital anomalies at the Instituto Materno Infantil, Bogota, Colombia]. / Frecuencia de anomalías congénitas en el Instituto Materno Infantil de Bogotá.

At the Instituto Materno Infantil (IMI) in Bogotá (Colombia), 5,686 births (5,597 live births and 89 stillbirths) were analyzed during two periods: from October, 1997, to April, 1998, and from July to November, 2000 (12 months). Congenital anomalies were detected in 4.4% of live newborn babies and in 7.8% of stillbirths. Major anomalies corresponded to 69% and mild anomalies to 31% (3% and 1.4% of all live births, respectively). The newborn babies with major anomalies, in comparison to the normal controls, had higher mortality at hospital discharge (p = 0.0001), lower average birth weight (p = 0.003), and family history of congenital anomalies (p = 0.0001). The only significant association for mild anomalies was with family history of congenital anomalies (p = 0.0001). The frequency of congenital anomalies was similar to that in other studies, although certain kinds of anomalies showed noticeable frequency differences. This may be a consequence of differences in record keeping or in detection methods.

Multiplex ligation-dependent probe amplification to subtelomeric rearrangements in idiopathic intellectual disability in Colombia.

BACKGROUND: A cause cannot be determined in 30% to 50% of patients with intellectual disability. Determining the etiology of intellectual disability is important and useful for pediatric neurologists, geneticists, pediatricians, and patients' families because it allows assessment of recurrence risk, appropriate genetic counseling, and focus on treatment options and prognosis. This study aims to determine the prevalence, origin, and characterization of subtelomeric rearrangements through the Multiplex Ligation-Dependent Probe Amplification method in pediatric patients with idiopathic intellectual disability. METHODS: A cross-sectional descriptive study was undertaken with patients seen in consultation at the neuropediatrics or genetic service of the Central Military Hospital, the Mercy' Hospital, or the Genetics Institute National University of Colombia. Patients were diagnosed with idiopathic intellectual disability between December 2010 and September 2011 and underwent a complete medical history, physical examination, and assessment to rule out other etiologies of intellectual disability. Then we applied the genetic test of Multiplex Ligation-Dependent Probe Amplification to each patient's sample of peripheral blood to determine subtelomeric rearrangements. RESULTS: We studied a group of 119 patients with idiopathic intellectual disability; Multiplex Ligation-Dependent Probe Amplification showed subtelomeric rearrangements in five. In the group with subtelomeric rearrangements, the most frequent results were de novo rearrangements (80%), deletion type (60%), moderate and severe intellectual disability (80%), minor phenotypic abnormalities (80%), and family history of neurological disorders (80%). No dependence relationship was observed between subtelomeric rearrangements and family history of neurological disorders, family history of intellectual disability, severity of intellectual disability, phenotypic abnormalities, and consanguinity. CONCLUSIONS: This study determined a prevalence of subtelomeric rearrangements of 4.2% in a group of Colombian pediatric patients with idiopathic intellectual disability using the genetic test Multiplex Ligation-Dependent Probe Amplification.

Ibuprofen inhibits migration and proliferation of human coronary artery smooth muscle cells by inducing a differentiated phenotype: role of peroxisome proliferator-activated receptor γ.

OBJECTIVES: The search for agents that are capable of preventing restenosis and reduce the risk of late thrombosis is of utmost importance. In this study we aim to evaluate the in vitro effects of ibuprofen on proliferation and migration of human coronary artery smooth muscle cells and on endothelial cells. METHODS: Cell proliferation was evaluated by trypan blue exclusion. Cell migration was assessed by wound-healing 'scratch' assay and time-lapse video microscopy. Protein expression was assessed by immunoblotting, and morphology by immunocytochemistry. The involvement of the PPARγ pathway was studied with the agonist troglitazone, and the use of selective antagonists such as PGF2α and GW9662. KEY FINDINGS: We demonstrate that ibuprofen inhibits proliferation and migration of HCASMCs and induces a switch in HCASMCs towards a differentiated and contractile phenotype, and that these effects are mediated through the PPARγ pathway. Importantly we also show that the effects of ibuprofen are cell type-specific as it does not affect migration and proliferation of endothelial cells. CONCLUSIONS: Taken together, our results suggest that ibuprofen could be an effective drug for the development of novel drug-eluting stents that could lead to reduced rates of restenosis and potentially other complications of DES implantation.

A clinical practice guideline for the prevention and treatment of peri-implant diseases / Guía de práctica clínica para la prevención y el tratamiento de enfermedades periimplantares

ABSTRACT Introduction: the incidence of peri-implant diseases is high, and their optimal management is still debated. The purpose was to explore the levels of available evidence and to suggest evidence-based recommendations for the treatment of peri-implant mucositis and peri-implantitis. Methods: a clinical practice guideline was developed using the Scottish Intercollegiate Guidelines Network (SIGN) criteria. A search strategy was formulated, and a critical review of the following evidence was performed: 1) prevention of peri-implant diseases, 2) treatment of peri-implant mucositis, and 3) treatment of peri-implantitis. Systematic reviews and randomized controlled clinical trials were the primary study types identified in the literature. Current levels of evidence were established and recommendations were provided. Results: a total of 67 articles were included. Regarding the prevention of peri-implant diseases, there is strong evidence for the involvement of patients in a regular maintenance program according to their risk profile. Regarding the treatment of peri-implant mucositis, infection control measures are recommended; controversy exists over the usefulness of antimicrobial agents, and there is evidence against the use of antibiotics. Selection of the peri-implantitis treatment method depends on the severity of the condition and patient-related factors. Resective and regenerative therapies may be used for treatment. The use of systemic antibiotics favors the response of clinical parameters. There is conditional evidence for the use of other adjunctive therapies. Conclusions: the best way to prevent peri-implantitis is to prevent peri-implant mucositis through adherence to supportive periodontal therapy. Treatment of peri-implant diseases depends on local and systemic conditions that affect the success of other treatment options.

RESUMEN Introducción: la incidencia de las enfermedades periimplantarias es alta, y todavía existe polémica en torno a su óptima administración. El propósito del presente estudio consistió en explorar los niveles de evidencia disponibles y ofrecer recomendaciones basadas en la evidencia para el tratamiento de la mucositis periimplantaria y la periimplantitis. Métodos: se elaboró una guía de práctica clínica utilizando los criterios de la Red de Directrices Intercolegiales Escocesas (Scottish Intercollegiate Guidelines Network, SIGN). Se formuló una estrategia de búsqueda y se realizó una revisión crítica de las siguientes evidencias: 1) prevención de enfermedades periimplantarias, 2) tratamiento de la mucositis periimplantaria y 3) tratamiento de la periimplantitis. Las revisiones sistemáticas y los ensayos clínicos controlados aleatorios fueron los principals tipos de estudio identificados en la literatura. Se establecieron los niveles actuales de evidencias y se ofrecieron recomendaciones. Resultados: se incluyeron 67 artículos. En cuanto a la prevención de enfermedades periimplantarias, hay claras evidencias de la participación de los pacientes en los programas de mantenimiento regular, de acuerdo con su perfil de riesgo. En cuanto al tratamiento de la mucositis periimplantaria, se recomiendan medidas de control de infecciones; existe controversia sobre la utilidad de los agentes antimicrobianos, y hay evidencia en contra del uso de antibióticos. La selección del método de tratamiento de la periimplantitis depende de la gravedad de la afección y de los factores relacionados con el paciente. Para el tratamiento se pueden utilizar terapias resectivas y regenerativas. El uso de antibióticos sistémicos favorece la respuesta de los parámetros clínicos. Hay evidencia condicional en cuanto al uso de otras terapias adyuvantes. Conclusiones: la mejor manera de prevenir la periimplantitis es prevenir la mucositis periimplantar mediante la adherencia a la terapia periodontal de apoyo. El tratamiento de las enfermedades periimplantarias depende de las condiciones locales y sistémicas que afectan el éxito de otras opciones de tratamiento.

Exploración preliminar del potencial de adopción de un paquete biotecnológico para el control de T. solanivora por parte de productores de papa de la región Cundiboyacense de Colombia / Preliminary exploration of the potential for adoption of a biotechnology package for the control of T. solanivora by potato producers in the Cundiboyacense region of Colombia

RESUMEN La papa es afectada por el ataque de Tecia solanivora que causa pérdidas hasta del 80%. Variedades genéticamente modificadas y biocontroladores, pueden ser usados para su manejo. Este estudio pretendió determinó el potencial socioeconómico de pequeños productores de papa de la región Cundiboyacense para la adopción de estas estrategias biotecnológicas, mediante encuestas cara a cara y el uso de metodologías como presupuestos parciales y modelo de regresión logística. Los resultados revelan que el tipo de semilla define la adopción, existiendo un interés por tecnologías que permitan el control de la plaga, por lo cual estarían dispuestos a pagar hasta un 30% más del valor actual por esta. La metodología de presupuestos parciales evidenció un efecto económico positivo en los diferentes escenarios planteados. Se concluyó que los pequeños productores de papa de los municipios analizados cuentan con un alto potencial socioeconómico para la adopción del paquete biotecnológico.

ABSTRACT The potato is affected by the attack of Tecia solanivora that causes losses of up to 80%. Genetically modified varieties and biocontrol agents, can be used for its control. This study aimed to determine the socioeconomic potential of small potato producers in the Cundiboyacense region for the adoption of these biotechnological strategies, through face-to-face surveys and the use of methodologies such as partial budgets and logistic regression model. The results reveal that the type of seed defines adoption, there being an interest in technologies that allow pest control, so they would be willing to pay up to 30% more of the current value for this. The methodology of partial budgets showed a positive economic effect in the different scenarios proposed. It was concluded that small potato producers in the municipalities analyzed have a high socioeconomic potential for the adoption of the biotechnology package.