Channel-Forming Activities in the Glycosomal Fraction from the Bloodstream Form of Trypanosoma brucei

Background: Glycosomes are a specialized form of peroxisomes (microbodies) present in unicellular eukaryotes that belong to the Kinetoplastea order, such as Trypanosoma and Leishmania species, parasitic protists causing severe diseases of livestock and humans in subtropical and tropical countries. The organelles harbour most enzymes of the glycolytic pathway that is responsible for substrate-level ATP production in the cell. Glycolysis is essential for bloodstream-form Trypanosoma brucei and enzymes comprising this pathway have been validated as drug targets. Glycosomes are surrounded by a single membrane. How glycolytic metabolites are transported across the glycosomal membrane is unclear. Methods/Principal Findings: We hypothesized that glycosomal membrane, similarly to membranes of yeast and mammalian peroxisomes, contains channel-forming proteins involved in the selective transfer of metabolites. To verify this prediction, we isolated a glycosomal fraction from bloodstream-form T.brucei and reconstituted solubilized membrane proteins into planar lipid bilayers. The electrophysiological characteristics of the channels were studied using multiple channel recording and single channel analysis. Three main channel-forming activities were detected with current amplitudes 70–80 pA, 20–25 pA, and 8–11 pA, respectively (holding potential +10 mV and 3.0 M KCl as an electrolyte). All channels were in fully open state in a range of voltages 6150 mV and showed no sub-conductance transitions. The channel with current amplitude 20–25 pA is anion-selective (P K+/P Cl2,0.31), while the other two types of channels are slightl

MANIFESTACIONES BUCALES MÁS FRECUENTES EN PACIENTES DIABÉTICOS ATENDIDOS EN EL INSTITUTO AUTONOMO HOSPITAL UNIVERSITARIO DE LOS ANDES

La diabetes mellitus (DM) es un desorden metabólico caracterizado por una hiperglicemia crónica debida a la resistencia periférica a la insulina, disfunción secretora de esta hormona o ambas. Lo cual produce alteraciones en el metabolismo de carbohidratos, lípidos y proteínas. El paciente diabético presentaciertas características que le confieren alto riesgo de padecer enfermedades cardiovasculares, cerebrales,renales, oculares y manifestaciones en cavidad bucal, en las que predominan las infecciones debido a laalteración del sistema inmunológico. Este artículo tiene como objetivo determinar las manifestacionesbucales más frecuentes de pacientes diabéticos que asisten a la consulta odontológica. Las cuales debenser tomadas en cuenta para realizar el diagnostico y tratamiento odontológico apropiado. En este sentido,se presenta el estudio de casos clínicos de 35 pacientes diabéticos atendidos en la Unidad de Endocrinología del Instituto Autónomo Hospital Universitario de Los Andes (I.A.H.U.L.A). El estudioconstó de la elaboración de la historia clínica con su respectivo examen clínico y examen radiográfico,monitoreo de niveles de glucosa en sangre, el establecimiento del diagnóstico y el tratamiento odontológico requerido en cada caso. Se encontró que, la gingivitis predominó en 97,1%, seguida decaries dental en 91,43% y periodontitis en 85,71% de los casos. Se concluyó que los pacientes diabéticos presentan alta incidencia de lesiones bucales, prevaleciendo una relación altamente significativa entre la periodontitis y los pacientes diabéticos mayores de 40 años.ABSTRACT Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia due to peripheralresistance to insulin, secretory dysfunction of this hormone or both, which cause alterations in the metabolism of carbohydrates, lipids and proteins. The diabetic patient shows certain characteristics that confer high risk for cardiovascular disease, cerebral, renal, and ocular manifestations in oral cavity, in which predominate infections due to alteration of the immune system. This article aims to explore themost common oral manifestations of diabetic patients attending the dental consultation that should betaken into account to make the diagnosis and appropriate dental treatment. In this sense, it presents astudy of 35 clinical cases of type 2 diabetic patients treated at the Unit of the Institute of EndocrinologyUniversity Hospital of Los Andes (IAHULA). The study consisted of the development of the medical history with their clinical and radiographic examination, monitoring of blood glucose levels, the establishment of diagnosis and dental treatment required for each case. It was found that gingivitis was predominant in 97.1% , followed by 91.43% in dental caries and periodontitis with 85.71% of cases. It was conclude

Comparison of qSOFA and SIRS for predicting adverse outcomes of patients with suspicion of sepsis outside the intensive care unit

Abstract Background The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Task Force recently introduced a new clinical score termed quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) for identification of patients at risk of sepsis outside the intensive care unit (ICU). We attempted to compare the discriminatory capacity of the qSOFA versus the Systemic Inflammatory Response Syndrome (SIRS) score for predicting mortality, ICU-free days, and organ dysfunction-free days in patients with suspicion of infection outside the ICU. Methods The Weill Cornell Medicine Registry and Biobank of Critically Ill Patients is an ongoing cohort of critically ill patients, for whom biological samples and clinical information (including vital signs before and during ICU hospitalization) are prospectively collected. Using such information, qSOFA and SIRS scores outside the ICU (specifically, within 8 hours before ICU admission) were calculated. This study population was therefore comprised of patients in the emergency department or the hospital wards who had suspected infection, were subsequently admitted to the medical ICU and were included in the Registry and Biobank. Results One hundred fifty-two patients (67% from the emergency department) were included in this study. Sixty-seven percent had positive cultures and 19% died in the hospital. Discrimination of in-hospital mortality using qSOFA [area under the receiver operating characteristic curve (AUC), 0.74; 95% confidence intervals (CI), 0.66–0.81] was significantly greater compared with SIRS criteria (AUC, 0.59; 95% CI, 0.51–0.67; p = 0.03). The qSOFA performed better than SIRS regarding discrimination for ICU-free days (p = 0.04), but not for ventilator-free days (p = 0.19), any organ dysfunction-free days (p = 0.13), or renal dysfunction-free days (p = 0.17). Conclusions In patients with suspected infection who eventually required admission to the ICU, qSOFA calculated before their ICU admission had greater accuracy than SIRS for predicting mortality and ICU-free days. However, it may be less clear whether qSOFA is also better than SIRS criteria for predicting ventilator free-days and organ dysfunction-free days. These findings may help clinicians gain further insight into the usefulness of qSOFA

Evolution and expression patterns of TCP genes in asparagales

ABSTARCT: CYCLOIDEA-like genes are involved in the symmetry gene network, limiting cell proliferation in the dorsal regions of bilateral flowers in core eudicots. CYC-like and closely related TCP genes (acronym for TEOSINTE BRANCHED1, CYCLOIDEA, and PROLIFERATION CELL FACTOR) have been poorly studied in Asparagales, the largest order of monocots that includes both bilateral flowers in Orchidaceae (ca. 25.000 spp) and radially symmetrical flowers in Hypoxidaceae (ca. 200 spp). With the aim of assessing TCP gene evolution in the Asparagales, we isolated TCP-like genes from publicly available databases and our own transcriptomes of Cattleya trianae (Orchidaceae) and Hypoxis decumbens (Hypoxidaceae). Our matrix contains 452 sequences representing the three major clades of TCP genes. Besides the previously identified CYC specific core eudicot duplications, our ML phylogenetic analyses recovered an early CIN-like duplication predating all angiosperms, two CIN-like Asparagales-specific duplications and a duplication prior to the diversification of Orchidoideae and Epidendroideae. In addition, we provide evidence of at least three duplications of PCF-like genes in Asparagales. While CIN-like and PCF-like genes have multiplied in Asparagales, likely enhancing the genetic network for cell proliferation, CYC-like genes remain as single, shorter copies with low expression. Homogeneous expression of CYC-like genes in the labellum as well as the lateral petals suggests little contribution to the bilateral perianth in C. trianae. CIN-like and PCF-like gene expression suggests conserved roles in cell proliferation in leaves, sepals and petals, carpels, ovules and fruits in Asparagales by comparison with previously reported functions in core eudicots and monocots. This is the first large scale analysis of TCP-like genes in Asparagales that will serve as a platform for in-depth functional studies in emerging model monocots