Targeted Metabolomics Shows That the Level of Glutamine, Kynurenine, Acyl-Carnitines and Lysophosphatidylcholines Is Significantly Increased in the Aqueous Humor of Glaucoma Patients.

The composition of the aqueous humor of patients with glaucoma is relevant to understand the underlying causes of the pathology. Information on the concentration of metabolites and small molecules in the aqueous humor of healthy subjects is limited. Among the causes of the limitations is the lack of healthy controls since, until recently, they were not surgically intervened; therefore, the aqueous humor of patients operated for cataract was used as a reference. Sixteen aqueous humor samples from healthy subjects undergoing refractive surgery and eight samples from glaucoma patients were used to assess the concentration of 188 compounds using chromatography and mass spectrometry. The concentration of 80 of the 188 was found to be reliable, allowing comparison of data from the two groups (glaucoma and control). The pattern found in the controls is similar to, but not the same as, that reported using samples from 'controls' undergoing cataract surgery. Comparing data from glaucoma patients and healthy subjects, 57 of the 80 compounds were significantly (p < 0.05) altered in the aqueous humor. Kynurenine and glutamine, but not glutamate, were significantly increased in the glaucoma samples. Furthermore, 10 compounds were selected considering a statistical score of p < 0.0001 and the degree of change of more than double or less than half. The level of C10 (decanoyl)-carnitine decreased, while the concentration of spermidine and various acyl-carnitines and lysophosphatidylcholines increased in glaucoma. Principal component analysis showed complete segregation of controls and cases using the data for the 10 selected compounds. The receiver operating characteristic curve these 10 compounds and for glutamine allowed finding cut-off values and significant sensitivity and specificity scores. The concentration of small metabolites in the aqueous humor of glaucoma patients is altered even when they take medication and are well controlled. The imbalance affects membrane components, especially those of the mitochondria, suggesting that mitochondrial abnormalities are a cause or consequence of glaucoma. The increase in glutamine in glaucoma is also relevant because it could be a means of keeping the concentration of glutamate under control, thus avoiding its potential to induce the death of neurons and retinal cells. Equally notable was the increase in kynurenine, which is essential in the metabolism of nicotine adenine dinucleotides

Self‐consistent intermediate Hamiltonians : A coupled cluster type formulation of the singles and doubles configuration interaction matrix dressing

This paper presents a new self‐consistent dressing of a singles and doubles configuration interaction matrix which insures size‐consistency, separability into closed‐shell subsystems if localized molecular orbitals (MOs) are used, and which includes all fourth order corrections. This method yields, among several schemes, a reformulation of the coupled cluster method, including fully the cluster operators of single and double excitations, and partially those of the triples (Bartlett’s algorithm named CCSDT‐1a). Further improvement can be easily included by adding exclusion principle violating corrections. Since it leads to a matrix diagonalization, the method behaves correctly in case of near degeneracies between the reference determinant and some doubles. Due to its flexibility this formulation offers the possibility of consistent combination with less expensive treatments for the study of very large [email protected] ; [email protected]

Bibliografía [Cuadernos del Instituto Antonio de Nebrija de estudios sobre la Universidad. 2004, nº 7]

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Escrotal circumference and skin flush sexual in florida male goat

Escrotal circumference (CE) by orquimetry and skin flush sexual (SFS) by observation in the inguino-escrotal skin in four Florida male goats were studied for 14 months. Seasonal variation was observed in CE, that was minor in autumn (30.84±0.24 cm) and maximun in spring (32.79 ±0.22 cm). Also, seasonal pattern was observed in SFS, with pale skin during winter (p<0.001). Light hours and temperature shown significant correlation with CE and SFS.En un grupo de cuatro machos cabríos de raza Florida se estudiaron las variaciones de la circunferencia escrotal (CE) y el grado de hiperemia inguino-escrotal o skin flush sexual (SFS) durante un periodo de 14 meses. Los resultados revelan una ligera variación estacional de la CE que es menor en otoño (30,84 ±0,24 cm.) y máxima en primavera (32,79±0,22 cm). El SFS presentó una distribución estacional, de manera que la coloración inguino-escrotal de la piel era más pálida durante el invierno (p<0,001). Tanto las horas de luz como la temperatura mostraron correlación significativa respecto a la CE y SFS

Solvents derived from glycerol modify classical regioselectivity in the enzymatic synthesis of disaccharides with Biolacta β-galactosidase

Green solvents made from glycerol change the classical regioselectivity of Biolacta No 5 β-galactosidase, from β(1→4) to β(1→6) linkages when a 2 M concentration was used. In order to explain these results, the non-proteic compounds present in the Biolacta preparation were separated by precipitation with ammonium sulfate and the remaining protein extract was used to set reactions with appropriate organic solvents to find that the regioselectivity towards the β(1→6) isomer is retained. According to proteomic analysis, a 98% homology between Streptococcus pneumoniae and Biolacta β-galactosidase preparation was found. With these data, molecular modelling was done which predicts a tridimensional interaction in the enzyme active site with the donor (GlcNAc) and the water-solvent mixture which explains this phenomenon. © 2011 The Royal Society of Chemistry.This work was supported by two research projects of the Spanish MICINN (Ministerio de Ciencia e Innovación de España) CTQ2009-11801 and CTQ2008-05138, and one European project (FP-62003-NMP-SMF-3, proposal 011774-2).Peer Reviewe

Soluble RAGE in COPD, with or without coexisting obstructive sleep apnoea

Background: Hypoxia can reduce the levels of soluble receptor for advanced glycation end-products (sRAGE), a new anti-inflammatory biomarker of COPD. We assessed sRAGE in patients with hypoxia-related diseases such as COPD, OSA and OSA-COPD overlap. Methods: Plasma levels of sRAGE were measured in 317 subjects at baseline (57 heathy nonsmokers HNS], 84 healthy smokers HS], 79 OSA, 62 COPD and 35 OSA-COPD overlap patients) and in 294 subjects after one year of follow-up (50 HNS, 74 HS, 77 OSA, 60 COPD and 33 overlap). Results: After adjusting for age, sex, smoking status and body mass index, sRAGE levels showed a reduction in OSA (- 12.5%, p = 0.005), COPD (- 14.8%, p < 0.001) and OSA-COPD overlap (- 12.3%, p = 0.02) compared with HNS. There were no differences when comparing sRAGE plasma levels between overlap patients and those with OSA or COPD alone. At follow-up, sRAGE levels did not change significantly in healthy subjects, COPD and OSA or OSA-COPD overlap nontreated with continuous positive airway pressure (CPAP). Moreover, in patients with OSA and OSA-COPD overlap who were treated with CPAP, sRAGE increased significantly. Conclusions: The levels of sRAGE are reduced in COPD and OSA. Treatment with CPAP appears to improve sRAGE levels in patients with OSA who also had COPD

Modification of corneal biomechanics and intraocular pressure following non-penetrating deep sclerectomy

Changes in the cornea can influence outcomes in patients with primary open-angle glaucoma (POAG). We aimed to evaluate the relevance of changes in corneal biomechanics and intraocular pressure (IOP) in patients undergoing non-penetrating deep sclerectomy (NPDS) with the Esnoper V2000 implant® (AJL Ophthalmic S.A., Gasteiz, Spain). We included 42 eyes of 42 patients with POAG scheduled for NPDS with the Esnoper V2000 implant. Biomechanical properties were measured by Ocular Response Analyzer® G3 (ORA; Reichert Inc., Depew, NY, USA). Corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated IOP (IOPcc), and Goldmann-correlated IOP (IOPg) were measured the day before surgery and on day 1, 7, and 30 and 2 and 3 months after surgery. CH initially increased, fell below the presurgical value at 30 days after the surgery, and increased again at 2 and 3 months. CRF, IOPcc, and IOPg decreased on the first day after surgery, then followed a trend of increasing but stayed below pre-surgery levels. All values reached statistical significance. While observed changes in corneal biomechanics after NPDS and Esnoper V2000 implant were significant, more studies are needed if we are to understand their influence on corneal biomechanics and their clinical relevance in POAG

Introducción del GLP en el mercado español de combustibles : un análisis a nivel local

El uso de combustibles ecológicos es un elemento fundamental para la reducción de la contaminación ambiental debido a la importante contribución que tiene el transporte terrestre en este problema. Tanto la Unión Europea como España están tomando medidas para reducir el uso de combustibles fósiles con subvenciones para la adquisición de coches ecológicos, ventaja fiscal para los combustibles menos contaminantes e impuestos para los combustibles habituales. En el mercado de combustible español, el consumo de GLP es muy inferior a su producción, nos hayamos en un problema de falta de demanda de este combustible por parte de los consumidores y de oferta por parte de las gasolineras. Se ha estimado el efecto de diferentes factores en la decisión de vender GLP en una gasolinera de España. Los resultados de la estimación muestran que tanto una mayor demanda potencial como una mayor dimensión de la gasolinera facilitan la adquisición de GLP, y por el contrario, la privatización de los buses locales dificulta la venta de este combustible

Vascular disease in COPD: systemic and pulmonary expression of PARC (Pulmonary and Activation-Regulated Chemokine)

Introduction: The role of Pulmonary and Activation-Regulated Chemokine (PARC) in the physiopathology of Chronic Obstructive Pulmonary Disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC in lung tissue and its relationship with the vascular remodeling of the systemic and pulmonary arteries of COPD subjects. Methods: To achieve this objective, protein and gene expression experiments, together with ELISA assays, were performed on the lung tissue, intercostal arteries and serum samples from COPD patients, non-obstructed smokers (NOS) and never-smokers (NS). Results: A total of 57 subjects were included in the analysis (23 COPD, 18 NOS and 16 NS). In the comparisons between groups, a significantly increased lung protein expression of PARC was observed in the COPD group compared to the NOS group (1.96±0.22 vs. 1.29±0.27, P-adjusted = 0.038). PARC was located predominantly in the smooth muscle cells of the remodeled pulmonary muscular arteries and the macrophage-rich area of the alveolar parenchyma. No differences were detected in PARC gene expression analyses. The protein content of PARC in the intercostal arteries were similar between groups, though little remodeling was observed in these arteries. Circulating levels of PARC were numerically higher in patients with COPD compared to NOS and NS. Conclusion: The results of the present study suggest an increased lung protein expression of PARC in COPD subjects. This protein was mainly localized in the smooth muscle cells of the pulmonary muscular arteries and was associated with the severity of intimal thickening, indicating its possible role in this remodeling process