Efecto antiinflamatorio de la izalpinina derivada de Chromolaena leivensis: edema de la pata inducido por λ-carragenina y modelo in silico

El flavonoide izalpinina se aisló de las partes aéreas de Chromolaena leivensis. Su determinación estructural se llevó a cabo mediante técnicas espectroscópicas de EM y RMN (1H, 13C). Se evaluó el efecto antiinflamatorio de este compuesto en un modelo de edema plantar inducido por carragenina en ratas. La inflamación de la pata se midió a intervalos de una hora durante siete horas tras la administración de -carragenano. Se evaluaron los niveles séricos de creatina quinasa (CK), obteniéndose resultados estadísticamente significativos con los tratamientos a dosis de 10 mg/kg (* p < 0,01) y 20 mg/kg (** p < 0,005). El efecto antiinflamatorio del compuesto se evaluó mediante pletismografía, y los resultados mostraron diferencias significativas en las tres concentraciones (10 mg/kg, 20 mg/kg, 40 mg/kg) en la primera y tercera hora tras el tratamiento. * p < 0,05; ** p < 0,001; **** p < 0,0001 frente al grupo de control negativo tratado con vehículo (DMSO). Por último, los análisis de acoplamiento molecular revelan que la izalpinina tiene una fuerte afinidad de unión con cinco proteínas diana implicadas en el proceso inflamatorio. El análisis mediante dinámica molecular permitió demostrar que los complejos ligando-proteína presentan una estabilidad aceptable, con valores de RMSD dentro del rango permitido.The flavonoid izalpinin was isolated from the aerial parts of Chromolaena leivensis. Its structural determination was carried out using MS and NMR spectroscopic techniques (1H, 13C). This compound was evaluated for its anti-inflammatory effect in a rat model on -carrageenan-induced plantar edema. Paw inflammation was measured at one-hour intervals for seven hours following the administration of -carrageenan. Serum creatine kinase (CK) levels were evaluated, obtaining statistically significant results with the treatments at doses of 10 mg/kg (* p < 0.01) and 20 mg/kg (** p < 0.005). The anti-inflammatory effect of the compound was evaluated by using plethysmography, and the results showed significant differences at the three concentrations (10 mg/kg, 20 mg/kg, 40 mg/kg) in the first and third hours after treatment. * p < 0.05; ** p < 0.001; **** p < 0.0001 vs. the negative control group treated with vehicle (DMSO). Lastly, molecular docking analyses reveal that izalpinin has a strong binding affinity with five target proteins involved in the inflammatory process. The analysis using molecular dynamics allowed demonstrating that the ligand–protein complexes present acceptable stability, with RMSD values within the allowed range

Género, clase y raza en América Latina: algunas aportaciones

Desde hace una década aproximadamente, se puede decir que en América Latina hay una búsqueda teórica para incorporar las relaciones de género a un esquema de análisis global de la realidad, donde se articulan con otras relaciones sociales generadas por otros conflictos que tienen relación con la clase, la edad, la raza, etc. Desde los inicios del feminismo, en este continente ha habido una sensibilidad especial por no aislar la problemática de las mujeres de la situación específica de estos países. Colonialismo, dependencia, imperialismo y desarrollo-subdesarrollo son los elementos claves de la situación crítica que viven estos pueblos desde hace siglos y que se caracteriza por la tremenda desigualdad social, las condiciones de pobreza en que vive la mayoría de la población y la violencia estructural. Ésta es la cara terrible y más conocida de América Latina, pero estos conflictos conviven con una gran riqueza material acumulada en pocas manos y otra riqueza que no se mide en dólares, más desconocida pero que está ahí para describirla, y es la gran fuerza y creatividad que hay en sus gentes y en su cultura popular. De ahí están saliendo las estrategias para sobrevivir en la crisis profunda que les afecta por una deuda realmente externa a sus intereses y las iniciativas de economía informal que han creado un sistema paralelo de mercado popular. En esta situación las mujeres están siendo la vanguardia de la lucha cotidiana por la sobrevivencia, y también han acumulado ya una buena parte de conocimiento sobre su realidad en relación con la sociedad en la que viven, con el fin de transformarla. Pero habría que añadir que la mochila que carga los deberes y los atributos de género aún es muy pesada y difícil de vaciar. Este es el reto a largo plazo por el que se apuesta de todas maneras en cada uno de los trabajos. Hay que señalar que aunque los textos proceden de autoras que geográficamente se relacionan con regiones diversas (mundo andino, centroamérica, cono sur), los contenidos de sus estudios no se centran mayoritariamente en casos específicos, sino que plantean cuestiones generalizables que a su vez se ejemplifican en experiencias concretas como es el caso de Colombia, Chile, Perú y Argentina. Esta selección de textos busca acercar a las/los interesados en el tema a las cuestiones que están en debate entre las investigadoras latinoamericanas y mostrar las aportaciones que desde allá se están haciendo al marco teórico feminista en un momento especialmente fructífero

Comparison of different treatments used for polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a disease that currently affects many women of reproductive age. In recent years, the incidence of PCOS has increased, affecting 4% of all women worldwide, with a prevalence of 6% in Mexico. PCOS is a condition characterized by different metabolic, reproductive and hormonal disorders such as hyperandrogenism, chronic anovulation, menorrhagia or infertility. Patients commonly develop clinical alterations such as hirsutism, acne and in some cases, they become overweight or obese. Different medications and therapeutic methods from different literatures were evaluated, both pharmacological such as inositol, metformin, resveratrol, simvastatin, dapagliflozin, which showed great improvement, decreasing the levels of hyperandrogenism in patients, as well as non-pharmacological, of which significant improvements were found with a change in lifestyle, such as exercise, ketogenic diet and herbal medications such as chamomile and cinnamon, which showed a positive change in patients. It is important to make a diffusion and early diagnosis of PCOS, since in this way it will be possible to have a timely treatment, which can be individualized according to the characteristics and needs of each patient

Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua, Mexico

BackgroundExposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures.ObjectiveThis study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk.MethodsWe analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008–2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine.ResultsAfter multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine.ConclusionsModerate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol.CitationMendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104–111; http://dx.doi.org/10.1289/ehp.140874

Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase ( AS3MT ) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level

Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures ≤50 ppb. Results suggest that iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism—and perhaps with susceptibility to iAs-associated disease—may vary in settings with exposure level

Urinary Aminopeptidase Activities as Early and Predictive Biomarkers of Renal Dysfunction in Cisplatin-Treated Rats

This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.This study was supported by a grant (R1/12/2010/66) from the University of Jaén with the participation of Caja Rural of Jaén, and from the Carlos III Health Institute of the Spanish Ministry of Health and Consumer Affairs (Red de Investigación Renal, REDinREN RD06/0016/0017 and RD07/0016/2008), “FEDER una manera de hacer Europa.

Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene

To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundació ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P=0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio=1.31; confidence interval 95% (1.19-1.44); P=9.74 × 10 - 9)

Associations between Arsenic Species in Exfoliated Urothelial Cells and Prevalence of Diabetes among Residents of Chihuahua, Mexico

Background: A growing number of studies link chronic exposure to inorganic arsenic (iAs) with the risk of diabetes. Many of these studies assessed iAs exposure by measuring arsenic (As) species in urine. However, this approach has been criticized because of uncertainties associated with renal function and urine dilution in diabetic individuals

Metabolomic Characteristics of Arsenic-Associated Diabetes in a Prospective Cohort in Chihuahua, Mexico

Chronic exposure to inorganic arsenic (iAs) has been linked to an increased risk of diabetes, yet the specific disease phenotype and underlying mechanisms are poorly understood. In the present study we set out to identify iAs exposure-associated metabolites with altered abundance in nondiabetic and diabetic individuals in an effort to understand the relationship between exposure, metabolomic response, and disease status. A nested study design was used to profile metabolomic shifts in urine and plasma collected from 90 diabetic and 86 nondiabetic individuals matched for varying iAs concentrations in drinking water, body mass index, age, and sex. Diabetes diagnosis was based on measures of fasting plasma glucose and 2-h blood glucose. Multivariable models were used to identify metabolites with altered abundance associated with iAs exposure among diabetic and nondiabetic individuals. A total of 132 metabolites were identified to shift in urine or plasma in response to iAs exposure characterized by the sum of iAs metabolites in urine (U-tAs). Although many metabolites were altered in both diabetic and nondiabetic 35 subjects, diabetic individuals displayed a unique response to iAs exposure with 59 altered metabolites including those that play a role in tricarboxylic acid cycle and amino acid metabolism. Taken together, these data highlight the broad impact of iAs exposure on the human metabolome, and demonstrate some specificity of the metabolomic response between diabetic and nondiabetic individuals. These data may provide novel insights into the mechanisms and phenotype of diabetes associated with iAs exposure

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population