Sarcoplasmic reticulum calcium ATPase is inhibited by organic vanadium coordination compounds: pyridine-2,6-dicarboxylatodioxovanadium(V), BMOV, and an amavadine analogue

Inorg Chem. 2008 Jul 7;47(13):5677-84. doi: 10.1021/ic702405dThe general affinity of the sarcoplasmic reticulum (SR) Ca (2+)-ATPase was examined for three different classes of vanadium coordination complexes including a vanadium(V) compound, pyridine-2,6-dicarboxylatodioxovanadium(V) (PDC-V(V)), and two vanadium(IV) compounds, bis(maltolato)oxovanadium(IV) (BMOV), and an analogue of amavadine, bis( N-hydroxylamidoiminodiacetato)vanadium(IV) (HAIDA-V(IV)). The ability of vanadate to act either as a phosphate analogue or as a transition-state analogue with enzymes' catalysis phosphoryl group transfer suggests that vanadium coordination compounds may reveal mechanistic preferences in these classes of enzymes. Two of these compounds investigated, PDC-V(V) and BMOV, were hydrolytically and oxidatively reactive at neutral pH, and one, HAIDA-V(IV), does not hydrolyze, oxidize, or otherwise decompose to a measurable extent during the enzyme assay. The SR Ca (2+)-ATPase was inhibited by all three of these complexes. The relative order of inhibition was PDC-V(V) > BMOV > vanadate > HAIDA-V(IV), and the IC 50 values were 25, 40, 80, and 325 microM, respectively. Because the observed inhibition is more potent for PDC-V(V) and BMOV than that of oxovanadates, the inhibition cannot be explained by oxovanadate formation during enzyme assays. Furthermore, the hydrolytically and redox stable amavadine analogue HAIDA-V(IV) inhibited the Ca (2+)-ATPase less than oxovanadates. To gauge the importance of the lipid environment, studies of oxidized BMOV in microemulsions were performed and showed that this system remained in the aqueous pool even though PDC-V(V) is able to penetrate lipid interfaces. These findings suggest that the hydrolytic properties of these complexes may be important in the inhibition of the calcium pump. Our results show that two simple coordination complexes with known insulin enhancing effects can invoke a response in calcium homeostasis and the regulation of muscle contraction through the SR Ca (2+)-ATPase

Clinical factors associated with high glycemic variability defined by coefficient of variation in patients with type 2 diabetes

Antecedentes: La Variabilidad Glucémica Alta (VHG) ha convertirse en un predictor más fuerte de hipoglucemia. Sin embargo, aún se desconocen los factores clínicos asociados con el VHG. Objetivo:Determinar las variables clínicas que se asociaron con un coeficiente de variación (CV) superior al 36% evaluado mediante monitorización continua de glucosa (MCG) en un grupo de pacientes con diabetes mellitus. Métodos: Se evaluó una cohorte de pacientes con diabetes tipo 2 (T2D). Se evaluaron variables demográficas, HbA1c, tasa de filtración glomerular (TFG) y régimen de tratamiento. Se realizó un análisis bivariado, para evaluar la asociación entre la variable resultado (CV > 36%) y cada una de las variables independientes. Se construyó un modelo multivariado para evaluar las asociaciones después de controlar las variables de confusión. Resultados:Se analizaron los datos de MCG de 274 pacientes. CV> 36% estuvo presente en 56 pacientes (20,4%). En el análisis bivariado se incluyeron variables demográficas y clínicas, como tiempo desde el diagnóstico, antecedente de hipoglucemia, A1c, FG y tratamiento instaurado. En el análisis multivariante, FG 9% (OR 2,81; IC 1,05,7,51; p:0,04) y antecedentes de hipoglucemia (OR 2,09; IC 1,02, 4,32; p: 0,04) se asociaron con VHG. El tratamiento con iDPP4 (OR 0,39; IC 0,19, 0,82; p: 0,01) y AGLP1 (OR 0,08; IC 0,01, 0,68; p: 0,02) se asoció inversamente con la VG. Conclusión:Variables clínicas como FG 9% y antecedentes de hipoglucemia se asocian a un VG alto. Nuestros datos sugieren que el uso de tecnología y tratamientos capaces de reducir la variabilidad glucémica podría ser útil en esta población para reducir el riesgo de hipoglucemia y mejorar el control glucémico.Q3Background: High glycemic Variability (HGV) has become a stronger predictor of hypoglycemia. However, clinical factors associate with HGV still are unknown. Objective: To determine clinical variables that were associated with a coefficient of variation (CV) above 36% evaluated by continuous glucose monitoring (CGM) in a group of patients with diabetes mellitus. Methods: A cohort of patients with type 2 diabetes (T2D) was evaluated. Demographic variables, HbA1c, glomerular filtration rate (GFR) and treatment regimen were assessed. A bivariate analysis was performed, to evaluate the association between the outcome variable (CV> 36%) and each of the independent variables. A multivariate model was constructed to evaluate associations after controlling for confounding variables. Results: CGM data from 274 patients were analyzed. CV> 36% was present in 56 patients (20.4%). In the bivariate analysis, demographic and clinical variables were included, such as time since diagnosis, hypoglycemia history, A1c, GFR and treatment established. In the multivariate analysis, GFR 9% (OR 2.81; CI 1.05,7.51; p:0.04) and hypoglycemia history (OR 2.09; CI 1.02,4.32; p:0.04) were associated with HGV. Treatment with iDPP4 (OR 0.39; CI 0.19,0.82; p:0.01) and AGLP1 (OR 0.08; CI 0.01,0.68; p:0.02) was inversely associated with GV. Conclusion: Clinical variables such as GFR 9% and a history of hypoglycemia are associated with a high GV. Our data suggest that the use of technology and treatments able to reduce glycemic variability could be useful in this population to reduce the risk of hypoglycemia and to improve glycemic control.Revista Internacional - Indexad

Charged Annular Disks and Reissner-Nordstr\"{o}m Type Black Holes from Extremal Dust

We present the first analytical superposition of a charged black hole with an annular disk of extremal dust. In order to obtain the solutions, we first solve the Einstein-Maxwell field equations for sources that represent disk-like configurations of matter in confomastatic spacetimes by assuming a functional dependence among the metric function, the electric potential and an auxiliary function,which is taken as a solution of the Laplace equation. We then employ the Lord Kelvin Inversion Method applied to models of finite extension in order to obtain annular disks. The structures obtained extend to infinity, but their total masses are finite and all the energy conditions are satisfied. Finally, we observe that the extremal Reissner-Nordstr\"{o}m black hole can be embedded into the center of the disks by adding a boundary term in the inversion.Comment: 17 revtex pages, 8 eps figure

Medical geography in the study of hepatitis A, in the Coffee-triangle region, Colombia, 2007-2011

Objectives: There are few studies of geographical characterization of viral hepatitis. For this reason, we after estimating the incidence rates for Hepatitis A (HAV), we developed epidemiological GIS-based maps for this viral disease, within a well-defined geographic region (the coffee triangle) in Colombia. Study design: A retrospective cross-sectional analysis of surveillance data and GIS-based developing of epidemiological maps. Methods: Surveillance cases data (2007-2011) were used to estimate annual incidence rates using reference population data, on hepatitis, to develop the first maps of HAV in the 53 municipalities of the coffee-triangle region of Colombia (departments Caldas, Quindio, Risaralda). GIS used was Kosmo® 3.1. To summarize and compare the data among municipalities and departments (as units of analysis) we generate indicators such as accumulated incidence rates (AIR) and incidence rates ratios. Results: 1518 HAV cases were reported, 47% from Quindío, 30% Caldas and 22% Risaralda. Quindio presented with the highest AIR (131.54) among all the administrative units under study (Caldas, AIR: 46.39; Risaralda, AIR: 37.62). Interestingly, the highest rates in Quindio, during the period, could be related to the increased number of cases reported in two municipalities from 2008 (Quimbaya, AIR ratio: 4.0 and Montenegro: 3.61). The causes that underlie this augmentation will be subject to further research. Conclusions: Incidence rates for HAV is still high in the region. Showing epidemiological data, particularly in maps would allow planning actions oriented to interventions at the different forms of transmission that this disease has, which is highly important for decisions in public health policies

Caracterización de las disparidades en exposición a plomo y cadmio en una población de mujeres gestantes, según posición socioeconómica en el oriente de la ciudad de Cali, entre 2009 y 2011 [recurso electrónico]

En este estudio se caracterizan las disparidades en exposición al plomo y cadmio en una población de mujeres gestantes, según posición socioeconómica en el oriente de la ciudad de Cali, entre 2009 y 2011. El proyecto formulado se realizó en el marco de un estudio en mujeres gestantes (Efecto de la exposición ambiental al plomo y cadmio en la ocurrencia del bajo peso al nacer (BPN y restricción del crecimiento intrauterino (RCIU) en una cohorte de mujeres gestantes de la ciudad de Cali, GEMA (2008)

Fish Oil Supplementation Reduces Inflammation but Does Not Restore Renal Function and Klotho Expression in an Adenine-Induced CKD Model

BACKGROUND: Chronic kidney disease and inflammation promote loss of Klotho expression. Given the well-established anti-inflammatory effects of omega-3 fatty acids, we aimed to investigate the effect of fish oil supplementation in a model of CKD. METHODS: Male C57BL/6 mice received supplementation with an adenine-enriched diet (AD, n = 5) or standard diet (CTL, n = 5) for 10 days. Two other experimental groups were kept under the adenine diet for 10 days. Following adenine withdrawal on the 11th day, the animals returned to a standard diet supplemented with fish oil (Post AD-Fish oil, n = 9) or not (Post AD-CTL, n = 9) for an additional period of 7 days. RESULTS: Adenine mice exhibited significantly higher mean serum urea, creatinine, and renal expression of the pro-inflammatory markers Interleukin-6 (IL-6), C-X-C motif chemokine 10 (CXCL10), and Interleukin-1β (IL-1β), in addition to prominent renal fibrosis and reduced renal Klotho gene expression compared to the control. Post AD-Fish oil animals demonstrated a significant reduction of IL-6, C-X-C motif chemokine 9 (CXCL9), and IL-1β compared to Post AD-CTL animals. However, serum creatinine, renal fibrosis, and Klotho were not significantly different in the fish oil-treated group. Furthermore, renal histomorphological changes such as tubular dilatation and interstitial infiltration persisted despite treatment. CONCLUSIONS: Fish oil supplementation reduced renal pro-inflammatory markers but was not able to restore renal function nor Klotho expression in an adenine-induced CKD model

Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina

© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Blood-vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs-sprouting angiogenesis and vascular remodeling-is established by a shift of collective front-to-rear polarity of endothelial cells in the mouse retina. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood-flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.Funding: European Research Council: C.A.F. (679368); X.T. (883739). European Commission: C.A.F. and M.O.B. (801423); X.T. and P.R.-C. (731957). H2020-MSCA-PF grants to M.G.-G. (797621) and M.O. (842498). Fondation LeDucq: C.A.F., A.E., and M.O.B. (17CVD03). EPSRC: M.O.B. (EP/T008806/1; EP/R029598/1). Fundação para a Ciência e Tecnologia: C.A.F. (PTDC/MED-PAT/31639/2017; PTDC/BIA-CEL/32180/2017; CEECIND/04251/2017). Spanish Ministry of Science and Innovation: P.R.-C. (PID2019-110298GB-I00); X.T. (PGC2018-099645-B-I00). Generalitat de Catalunya: X.T. and P.R.-C. (2017-SGR-1602). La Caixa Foundation: X.T. and P.R.-C. (LCF/PR/HR20/52400004). Fundació la Marató de TV3: X.T. (201903-30-31-32). EMBO: L.M.F. (ALTF 2-2018)info:eu-repo/semantics/publishedVersio

The RNA Binding Protein SAM68 Transiently Localizes in the Chromatoid Body of Male Germ Cells and Influences Expression of Select MicroRNAs

The chromatoid body (CB) is a unique structure of male germ cells composed of thin filaments that condense into a perinuclear organelle after meiosis. Due to the presence of proteins involved in different steps of RNA metabolism and of different classes of RNAs, including microRNAs (miRNAs), the CB has been recently suggested to function as an RNA processing centre. Herein, we show that the RNA binding protein SAM68 transiently localizes in the CB, in concomitance with the meiotic divisions of mouse spermatocytes. Precise staging of the seminiferous tubules and co-localization studies with MVH and MILI, two well recognized CB markers, documented that SAM68 transiently associates with the CB in secondary spermatocytes and early round spermatids. Furthermore, although SAM68 co-immunoprecipitated with MVH in secondary spermatocytes, its ablation did not affect the proper localization of MVH in the CB. On the other hand, ablation of the CB constitutive component MIWI did not impair association of SAM68 with the CB. Isolation of CBs from Sam68 wild type and knockout mouse testes and comparison of their protein content by mass spectrometry indicated that Sam68 ablation did not cause overall alterations in the CB proteome. Lastly, we found that SAM68 interacts with DROSHA and DICER in secondary spermatocytes and early round spermatids and that a subset of miRNAs were altered in Sam68−/−germ cells. These results suggest a novel role for SAM68 in the miRNA pathway during spermatogenesis