Enolase from Trypanosoma cruzi is inhibited by its interaction with metallocarboxypeptidase-1 and a putative acireductone dioxygenase.

Purification of enolase (ENO) from the cytosol of Trypanosoma cruzi indicated that it may interact with at least five other proteins. Two of them were identified as metallocarboxypeptidase-1 (TcMCP-1) and a putative acireductone dioxygenase (ARDp). Subcellular localization studies confirmed the presence of ARDp in the cytosol, as is the case for ENO and TcMCP-1. Analysis of the ARDp sequence showed that this protein has two domains, an N-terminal ARD and a C-terminal TRP14 (thioredoxin-related protein) domain. The interactions between ENO, TcMCP-1 and ARDp were confirmed for the natural proteins from the trypanosome (using size-exclusion chromatography and co-immunoprecipitation from a cytosolic fraction) and recombinant forms (using ELISA ligand-binding assay and ENO activity assays). The ELISA ligand-binding assays permitted to verify the optimal physicochemical conditions for the interactions (representative for the physiological conditions) and to determine the affinity constants (Kd): ENO/ARDp: 9.54 ±â€¯0.82 nM, ARDp/ENO 10.05 ±â€¯1.11 nM, and ENO/TcMCP-1: 5.66 ±â€¯0.61 nM. The data also show that the interaction between TcMCP-1 and ARDp is mediated by ENO acting as a "bridge". Furthermore, considerable inhibition of the ENO activity, up to 85%, is observed when the enzyme interacts with TcMCP-1 and ARDp simultaneously. All these data confirm that the interaction between ENO, TcMCP-1 and ARDp, occurring in T. cruzi's cytosol, modulates the ENO activity and suggest a possible physiological mechanism for regulation of the ENO activity by the protein-protein interaction.

[Carbapenem resistance in Pseudomonas aeruginosa isolated from urine cultures: prevalence and risk factors]. / Resistencia a carbapenemas en Pseudomonas aeruginosa aisladas en urocultivos: prevalencia y factores de riesgo.

OBJECTIVE: Pseudomonas aeruginosa is a non-fermentative gram-negative bacillus with a great ability to develop resistance to multiple antibiotics, including carbapenems, which is a growing problem worldwide. The aim of this study was to analyse the prevalence of carbapenem-resistant P. aeruginosa (CRPA) in urine cultures and to determine the risk factors associated with the development of carbapanem resistance. METHODS: Positive urine cultures to P. aeruginosa between September 2012 and September 2014 were identified. We excluded repetitive cultures from the same patient. We created a database with different variables, including antimicrobial resistance. The prevalence of carbapenem resistance and the risk factors for growth of CRPA were analysed. RESULTS: Ninety-one patients with positive urine cultures to P. aeruginosa were included. The prevalence of CRPA was 22%. The risk factors to CRPA infection in the univariate analysis were: congestive heart failure (p=0.02), previous treatment with ampicillin (p=0.04), meropenem (p=0.04), piperacillin-tazobactam (p=0.01), trimethoprim-sulfamethoxazole (p= 0.01) and previous treatment with more than one antibiotic (p<0.01). Only congestive heart failure (p<0.01) and previous treatment with more than one antibiotic (p<0.01) showed statistically significant differences in the multivariate analysis. CONCLUSIONS: The prevalence of CRPA in urine cultures is high in our population. We should assess the presence of risk factors as previous treatment with more than one antibiotic or comorbidities such as heart failure, in order to select an appropriate empirical treatment in patients with severe urinary tract infections.

Lesser devil rays Mobula cf. hypostoma from Venezuela are almost twice their previously reported maximum size and may be a new sub-species.

Three rays opportunistically obtained near Margarita Island, Venezuela, were identified as lesser devil rays Mobula cf. hypostoma, but their disc widths were between 207 and 230 cm, which is almost double the reported maximum disc width of 120 cm for this species. These morphometric data suggest that lesser devil rays are either larger than previously recognized or that these specimens belong to an unknown sub-species of Mobula in the Caribbean Sea. Better data are needed to describe the distribution, phenotypic variation and population structure of this poorly known species.

EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma.

Ewing sarcoma is characterized by chromosomal translocations fusing the EWS gene with various members of the ETS family of transcription factors, most commonly FLI1. EWS-FLI1 is an aberrant transcription factor driving Ewing sarcoma tumorigenesis by either transcriptionally inducing or repressing specific target genes. Herein, we showed that Sprouty 1 (SPRY1), which is a physiological negative feedback inhibitor downstream of fibroblast growth factor (FGF) receptors (FGFRs) and other RAS-activating receptors, is an EWS-FLI1 repressed gene. EWS-FLI1 knockdown specifically increased the expression of SPRY1, while other Sprouty family members remained unaffected. Analysis of SPRY1 expression in a panel of Ewing sarcoma cells showed that SPRY1 was not expressed in Ewing sarcoma cell lines, suggesting that it could act as a tumor suppressor gene in these cells. In agreement, induction of SPRY1 in three different Ewing sarcoma cell lines functionally impaired proliferation, clonogenic growth and migration. In addition, SPRY1 expression inhibited extracellular signal-related kinase/mitogen-activated protein kinase (MAPK) signaling induced by serum and basic FGF (bFGF). Moreover, treatment of Ewing sarcoma cells with the potent FGFR inhibitor PD-173074 reduced bFGF-induced proliferation, colony formation and in vivo tumor growth in a dose-dependent manner, thus mimicking SPRY1 activity in Ewing sarcoma cells. Although the expression of SPRY1 was low when compared with other tumors, SPRY1 was variably expressed in primary Ewing sarcoma tumors and higher expression levels were significantly associated with improved outcome in a large patient cohort. Taken together, our data indicate that EWS-FLI1-mediated repression of SPRY1 leads to unrestrained bFGF-induced cell proliferation, suggesting that targeting the FGFR/MAPK pathway can constitute a promising therapeutic approach for this devastating disease.

Dabigatrán: experiencia en la práctica clínica habitual / Dabigatran: experience in standard clinical practice

Introducción y objetivos. Dabigatrán es un fármaco anticoagulante, inhibidor directo de la trombina, aprobado para la prevención de ictus isquémico secundario a fibrilación auricular no valvular. El objetivo de este estudio fue determinar la eficacia de dabigatrán en la práctica clínica para la prevención de eventos isquémicos cerebrales asociados a fibrilación auricular no valvular, así como su perfil de tolerancia y seguridad. Material y métodos. Estudio descriptivo y retrospectivo en el que se incluyó a todos los pacientes que iniciaron tratamiento anticoagulante con dabigatrán entre los meses de noviembre de 2011 y septiembre de 2012. Se realizó seguimiento desde el comienzo del tratamiento hasta junio de 2013. Se determinó la incidencia de eventos isquémicos de origen cerebral, cardíaco y periférico, así como la aparición de efectos adversos y complicaciones hemorrágicas, determinando su localización y gravedad. Resultados. Se analizó a 316 pacientes con una edad media de 76,46±8,37 años, de los que el 53,5% eran varones. Dos pacientes (0,55/100 pacientes-año) presentaron ictus isquémico (incluyendo una amaurosis fugax). Ocho (2,18/100 pacientes-año) tuvieron un evento adverso isquémico, que fue de origen cardíaco en 5 (1,36/100 pacientes-año) casos y periférico en 3 (0,81/100 pacientes-año). Cuarenta (10,91/100 pacientes-año) tuvieron una complicación hemorrágica: 32 hemorragias menores (8,73/100 pacientes-año) y 8 mayores (2,18/100 pacientes-año). Conclusiones. Dabigatrán en la práctica clínica habitual es eficaz en la prevención de ictus y presenta un perfil de seguridad similar al reportado en los ensayos clínicos (AU)

Introduction and objectives. Dabigatran is an anticoagulant drug and a direct thrombin inhibitor and has been approved for the prevention of ischaemic stroke secondary to nonvalvularauricular auricular fibrillation. The aim of this study was to determine the efficacy of dabigatran in clinical practice for preventing cerebral ischaemic events associated with nonvalvularauricular auricular fibrillation, as well as its tolerance and safety profile. Material and methods. A descriptive and retrospective study was conducted, which included all patients who started anticoagulant treatment with dabigatran between November 2011 and September 2012. Follow-up was performed from the start of treatment until June 2013. The incidence of ischaemic events of cerebral, cardiac and peripheral origin was recorded, as was the onset of adverse effects and haemorrhagic complications, whose location and severity were determined. Results. We analysed 316 patients, with a mean age of 76.46±8.37 years, of whom 53.5% were men. Two patients (0.55/100 patient-years) presented ischaemic stroke (including one amaurosis fugax). Eight (2.18/100 patient-years) patients had an adverse ischaemic event, whose origin was cardiac in 5 (1.36/100 patient-years) cases and peripheral in 3 (0.81/100 patient-years). Forty (10.91/100 patient-years) patients had a haemorrhagic complication: 32 minor (8.73/100 patient-years) and 8 major (2.18/100 patient-years) haemorrhages. Conclusions. Dabigatran is effective in standard clinical practice in preventing stroke and has a safety profile similar to that reported in the clinical trials (AU)

Dabigatran: Experience in standard clinical practice. / Dabigatrán: experiencia en la práctica clínica habitual.

INTRODUCTION AND OBJECTIVES: Dabigatran is an anticoagulant drug and a direct thrombin inhibitor and has been approved for the prevention of ischaemic stroke secondary to nonvalvularauricular auricular fibrillation. The aim of this study was to determine the efficacy of dabigatran in clinical practice for preventing cerebral ischaemic events associated with nonvalvularauricular auricular fibrillation, as well as its tolerance and safety profile. MATERIAL AND METHODS: A descriptive and retrospective study was conducted, which included all patients who started anticoagulant treatment with dabigatran between November 2011 and September 2012. Follow-up was performed from the start of treatment until June 2013. The incidence of ischaemic events of cerebral, cardiac and peripheral origin was recorded, as was the onset of adverse effects and haemorrhagic complications, whose location and severity were determined. RESULTS: We analysed 316 patients, with a mean age of 76.46±8.37 years, of whom 53.5% were men. Two patients (0.55/100 patient-years) presented ischaemic stroke (including one amaurosis fugax). Eight (2.18/100 patient-years) patients had an adverse ischaemic event, whose origin was cardiac in 5 (1.36/100 patient-years) cases and peripheral in 3 (0.81/100 patient-years). Forty (10.91/100 patient-years) patients had a haemorrhagic complication: 32 minor (8.73/100 patient-years) and 8 major (2.18/100 patient-years) haemorrhages. CONCLUSIONS: Dabigatran is effective in standard clinical practice in preventing stroke and has a safety profile similar to that reported in the clinical trials.

Distrofia en huella dactilar: brotes de astigmatismo irregular y su demostración topográfica / Fingerprint microcystic dystrophy: Episodes of irregular astigmatism and their topographical representation

Caso clínico: Varón de 44 años con brotes indoloros de visión borrosa sin repercusión oftalmológica visible inicialmente. Tras uno de sus episodios, se visualiza en polo anterior imágenes en huella digital así como cambios corneales, paquimétricos y topográficos que originan cambios refractivos sintomáticos. Discusión: La distrofia en huella dactilar es una entidad diagnosticada por erosiones corneales recurrentes. Su base patogénica, una membrana basal epitelial alterada, favorece la separación del epitelio corneal de las capas subyacentes. En la medida que ésta sea total o parcial ocasionará erosiones corneales recurrentes o, con menor frecuencia, episodios de visión borrosa por edema y engrosamiento corneal(AU)

Case Study: A 44 year-old male patient suffering from painless bouts of blurred vision and with no visible ophthalmological repercussions initially. After one of these clinical episodes we managed to visualise fingerprint images in the anterior pole, as well as corneal, pachymetric and topographical changes, which in turn produce the symptomatic refractive changes. Discussion: Fingerprint keratopathy is a condition diagnosed through recurring corneal erosion. The pathogenic origin of the condition-an altered epithelial basal membrane- may encourage the separation of the corneal epithelium from its underlying layers. Depending on whether this separation is partial or total, this will lead to spontaneous corneal erosion or, less frequently, episodes of blurred vision caused by oedema and corneal swelling(AU)

[Fingerprint microcystic dystrophy: Episodes of irregular astigmatism and their topographical representation]. / Distrofia en huella dactilar: brotes de astigmatismo irregular y su demostración topográfica.

CASE STUDY: A 44 year-old male patient suffering from painless bouts of blurred vision and with no visible ophthalmological repercussions initially. After one of these clinical episodes we managed to visualise fingerprint images in the anterior pole, as well as corneal, pachymetric and topographical changes, which in turn produce the symptomatic refractive changes. DISCUSSION: Fingerprint keratopathy is a condition diagnosed through recurring corneal erosion. The pathogenic origin of the condition-an altered epithelial basal membrane- may encourage the separation of the corneal epithelium from its underlying layers. Depending on whether this separation is partial or total, this will lead to spontaneous corneal erosion or, less frequently, episodes of blurred vision caused by oedema and corneal swelling.

Presente de la historia clínica electrónica en nefrología ambulatoria / Present of the electronic clinical record in outpatient nephrology

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