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1.
J Biol Chem ; 299(6): 104764, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37121548

RESUMEN

N-acyl amino acids are a large family of circulating lipid metabolites that modulate energy expenditure and fat mass in rodents. However, little is known about the regulation and potential cardiometabolic functions of N-acyl amino acids in humans. Here, we analyze the cardiometabolic phenotype associations and genomic associations of four plasma N-acyl amino acids (N-oleoyl-leucine, N-oleoyl-phenylalanine, N-oleoyl-serine, and N-oleoyl-glycine) in 2351 individuals from the Jackson Heart Study. We find that plasma levels of specific N-acyl amino acids are associated with cardiometabolic disease endpoints independent of free amino acid plasma levels and in patterns according to the amino acid head group. By integrating whole genome sequencing data with N-acyl amino acid levels, we identify that the genetic determinants of N-acyl amino acid levels also cluster according to the amino acid head group. Furthermore, we identify the CYP4F2 locus as a genetic determinant of plasma N-oleoyl-leucine and N-oleoyl-phenylalanine levels in human plasma. In experimental studies, we demonstrate that CYP4F2-mediated hydroxylation of N-oleoyl-leucine and N-oleoyl-phenylalanine results in metabolic diversification and production of many previously unknown lipid metabolites with varying characteristics of the fatty acid tail group, including several that structurally resemble fatty acid hydroxy fatty acids. These studies provide a structural framework for understanding the regulation and disease associations of N-acyl amino acids in humans and identify that the diversity of this lipid signaling family can be significantly expanded through CYP4F-mediated ω-hydroxylation.


Asunto(s)
Aminoácidos , Familia 4 del Citocromo P450 , Ácidos Oléicos , Humanos , Aminoácidos/sangre , Aminoácidos/química , Enfermedades Cardiovasculares , Familia 4 del Citocromo P450/metabolismo , Ácidos Grasos/metabolismo , Leucina , Fenilalanina , Ácidos Oléicos/sangre
2.
Mov Disord ; 39(2): 400-410, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38314870

RESUMEN

BACKGROUND: Congenital mirror movements (CMM) is a rare neurodevelopmental disorder characterized by involuntary movements from one side of the body that mirror voluntary movements on the opposite side. To date, five genes have been associated with CMM, namely DCC, RAD51, NTN1, ARHGEF7, and DNAL4. OBJECTIVE: The aim of this study is to characterize the genetic landscape of CMM in a large group of 80 affected individuals. METHODS: We screened 80 individuals with CMM from 43 families for pathogenic variants in CMM genes. In large CMM families, we tested for presence of pathogenic variants in multiple affected and unaffected individuals. In addition, we evaluated the impact of three missense DCC variants on binding between DCC and Netrin-1 in vitro. RESULTS: Causal pathogenic/likely pathogenic variants were found in 35% of probands overall, and 70% with familial CMM. The most common causal gene was DCC, responsible for 28% of CMM probands and 80% of solved cases. RAD51, NTN1, and ARHGEF7 were rare causes of CMM, responsible for 2% each. Penetrance of CMM in DCC pathogenic variant carriers was 68% and higher in males than females (74% vs. 54%). The three tested missense variants (p.Ile164Thr; p.Asn176Ser; and p.Arg1343His) bind Netrin-1 similarly to wild type DCC. CONCLUSIONS: A genetic etiology can be identified in one third of CMM individuals, with DCC being the most common gene involved. Two thirds of CMM individuals were unsolved, highlighting that CMM is genetically heterogeneous and other CMM genes are yet to be discovered. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Asunto(s)
Discinesias , Trastornos del Movimiento , Masculino , Femenino , Humanos , Netrina-1/genética , Receptor DCC/genética , Trastornos del Movimiento/genética , Mutación Missense/genética , Factores de Intercambio de Guanina Nucleótido Rho/genética
3.
Circ Res ; 131(7): 601-615, 2022 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-36052690

RESUMEN

BACKGROUND: Racial differences in metabolomic profiles may reflect underlying differences in social determinants of health by self-reported race and may be related to racial disparities in coronary heart disease (CHD) among women in the United States. However, the magnitude of differences in metabolomic profiles between Black and White women in the United States has not been well-described. It also remains unknown whether such differences are related to differences in CHD risk. METHODS: Plasma metabolomic profiles were analyzed using liquid chromatography-tandem mass spectrometry in the WHI-OS (Women's Health Initiative-Observational Study; 138 Black and 696 White women), WHI-HT trials (WHI-Hormone Therapy; 156 Black and 1138 White women), MESA (Multi-Ethnic Study of Atherosclerosis; 114 Black and 219 White women), JHS (Jackson Heart Study; 1465 Black women with 107 incident CHD cases), and NHS (Nurses' Health Study; 2506 White women with 136 incident CHD cases). First, linear regression models were used to estimate associations between self-reported race and 472 metabolites in WHI-OS (discovery); findings were replicated in WHI-HT and validated in MESA. Second, we used elastic net regression to construct a racial difference metabolomic pattern (RDMP) representing differences in the metabolomic patterns between Black and White women in the WHI-OS; the RDMP was validated in the WHI-HT and MESA. Third, using conditional logistic regressions in the WHI (717 CHD cases and 719 matched controls), we examined associations of metabolites with large differences in levels by race and the RDMP with risk of CHD, and the results were replicated in Black women from the JHS and White women from the NHS. RESULTS: Of the 472 tested metabolites, levels of 259 (54.9%) metabolites, mostly lipid metabolites and amino acids, significantly differed between Black and White women in both WHI-OS and WHI-HT after adjusting for baseline characteristics, socioeconomic status, lifestyle factors, baseline health conditions, and medication use (false discovery rate <0.05); similar trends were observed in MESA. The RDMP, composed of 152 metabolites, was identified in the WHI-OS and showed significantly different distributions between Black and White women in the WHI-HT and MESA. Higher RDMP quartiles were associated with an increased risk of incident CHD (odds ratio=1.51 [0.97-2.37] for the highest quartile comparing to the lowest; Ptrend=0.02), independent of self-reported race and known CHD risk factors. In race-stratified analyses, the RDMP-CHD associations were more pronounced in White women. Similar patterns were observed in Black women from the JHS and White women from the NHS. CONCLUSIONS: Metabolomic profiles significantly and substantially differ between Black and White women and may be associated with CHD risk and racial disparities in US women.


Asunto(s)
Enfermedad Coronaria , Aminoácidos , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Femenino , Hormonas , Humanos , Lípidos , Factores de Riesgo , Estados Unidos/epidemiología
4.
PLoS Comput Biol ; 19(5): e1011161, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37253069

RESUMEN

In the plant sciences, results of laboratory studies often do not translate well to the field. To help close this lab-field gap, we developed a strategy for studying the wiring of plant traits directly in the field, based on molecular profiling and phenotyping of individual plants. Here, we use this single-plant omics strategy on winter-type Brassica napus (rapeseed). We investigate to what extent early and late phenotypes of field-grown rapeseed plants can be predicted from their autumnal leaf gene expression, and find that autumnal leaf gene expression not only has substantial predictive power for autumnal leaf phenotypes but also for final yield phenotypes in spring. Many of the top predictor genes are linked to developmental processes known to occur in autumn in winter-type B. napus accessions, such as the juvenile-to-adult and vegetative-to-reproductive phase transitions, indicating that the yield potential of winter-type B. napus is influenced by autumnal development. Our results show that single-plant omics can be used to identify genes and processes influencing crop yield in the field.


Asunto(s)
Brassica napus , Brassica napus/genética , Hojas de la Planta/genética , Fenotipo , Expresión Génica
5.
Actas Esp Psiquiatr ; 52(2): 72-82, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38622005

RESUMEN

INTRODUCTION: The increase in suicidal behavior among adolescents under 17 years of age in Catalonia between 2019 and 2022 has gone from 473 to 1425 cases, which entails a new healthcare challenge. The objective of the article is to explain the procedure and intervention of the Rapid Response Unit (RRU) for children and adolescents at risk of suicide. The RRU is a multidisciplinary unit designed to prevent relapse and increase link-up to treatment. The cases attended in its 14 months of operation are described. METHODOLOGY: 24 patients, 18 females and 6 males aged between 12 and 17 years, attended for the first time at the Child and Adolescent Health Centre of Cornellà for activation of the Suicide Risk Code (CRS) in hospital emergency departments during the period studied. RESULTS: After the intervention, high suicidal risk decreased from 29.17% to 0%, medium risk decreased from 37.5% to 20.83% and low risk increased from 33.33% to 79.17%. In addition, there was only one new CRS activation in the 3 months following the first activation. In the RRU, care was intensive: 52.7% of cases with visits once a week and more than once a week in 24.9%. During the intervention months 100% of cases were linked and no interruptions occurred. CONCLUSIONS: Rapid Response Unit (RRU) decreases the risk of recurrence of suicidal behavior and ensures therapeutic linkage.


Asunto(s)
Intento de Suicidio , Suicidio , Masculino , Niño , Femenino , Humanos , Adolescente , Ideación Suicida , Recurrencia , Servicio de Urgencia en Hospital
6.
Circulation ; 145(5): 357-370, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34814699

RESUMEN

BACKGROUND: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. METHODS: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). RESULTS: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10-11. These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, ß=0.61±0.05, P=3.27×10-30) and MMP-3 (ß=-0.60±0.05, P=1.67×10-32), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, ß=0.34±0.04, P=1.34×10-17) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. CONCLUSIONS: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Estudio de Asociación del Genoma Completo/métodos , Proteoma/metabolismo , Adulto , Población Negra , Femenino , Humanos , Masculino
7.
J Org Chem ; 88(15): 11102-11110, 2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37485981

RESUMEN

The physical factors governing the catalysis in Lewis acid-promoted carbonyl-ene reactions have been explored in detail quantum chemically. It is found that the binding of a Lewis acid to the carbonyl group directly involved in the transformation greatly accelerates the reaction by decreasing the corresponding activation barrier up to 25 kcal/mol. The Lewis acid makes the process much more asynchronous and the corresponding transition state less in-plane aromatic. The remarkable acceleration induced by the catalyst is ascribed, by means of the activation strain model and the energy decomposition analysis methods, mainly to a significant reduction of the Pauli repulsion between the key occupied π-molecular orbitals of the reactants and not to the widely accepted stabilization of the LUMO of the enophile.

8.
Phys Chem Chem Phys ; 25(40): 27276-27292, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37791459

RESUMEN

The bonding structures of tetrahedrane, phosphatetrahedrane, diphosphatetrahedrane and triphosphatetrahedrane are studied by employing an intrinsic quasi-atomic orbital analysis. Ethane, cyclopropane and tetrahedral P4 are employed as reference systems. The orbital analysis is paired with the computation of strain energies via isodesmic reactions. The results show that the increase in geometric strain upon transition from ethane to cyclopropane to tetrahedrane weakens the CC bonds, despite leading to shorter C-C interatomic distances. With the increase in strain, the orbitals centered on C and involved in the bonding of the cage structure are observed to have elevated p-character, and the orbital structure of C deviates from sp3 hybridization. The systematic substitution of CH groups by P atoms in the cage structure of tetrahedrane leads to stronger CC bonds, larger angles in the cage structures of the resulting phosphatetrahedranes, lower p-character in the orbitals involved in the bonding of the cages, and lower strain energies. It is found that P is more amenable to strained molecular arrangements than is C, and that the propensity of a given atom to hybridize s and p functions, or the lack thereof, has implications in the stability of molecules with strained geometries. The combination of the calculations presented here with the existing literature provides insight into the apparent propensity of tetrahedrane and P4 to 'break' their tetrahedral structures. Trends in the bonding interactions, such as bond strengths, s- and p-orbital characters and charge transfer are identified and related to the strain energy observed in each of the analyzed systems.

9.
Molecules ; 28(12)2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37375401

RESUMEN

Developing new types of effective antimicrobial compounds derived from natural products is of interest for the food industry. Some analogs to A-type proanthocyanidins have shown promising antimicrobial and antibiofilm activities against foodborne bacteria. We report herein the synthesis of seven additional analogs with NO2 group at A-ring and their abilities for inhibiting the growth and the biofilm formation by twenty-one foodborne bacteria. Among them, analog 4 (one OH at B-ring; two OHs at D-ring) showed the highest antimicrobial activity. The best results with these new analogs were obtained in terms of their antibiofilm activities: analog 1 (two OHs at B-ring; one OH at D-ring) inhibited at least 75% of biofilm formation by six strains at all of the concentrations tested, analog 2 (two OHs at B-ring; two OHs at D-ring; one CH3 at C-ring) also showed antibiofilm activity on thirteen of the bacteria tested, and analog 5 (one OH at B-ring; one OH at D-ring) was able to disrupt preformed biofilms in eleven strains. The description of new and more active analogs of natural compounds and the elucidation of their structure-activity relationships may contribute to the active development of new food packaging for preventing biofilm formation and lengthening the food shelf life.


Asunto(s)
Antiinfecciosos , Productos Biológicos , Proantocianidinas , Antibacterianos/farmacología , Proantocianidinas/farmacología , Productos Biológicos/farmacología , Antiinfecciosos/farmacología , Biopelículas , Bacterias , Pruebas de Sensibilidad Microbiana
10.
Entropy (Basel) ; 25(5)2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37238464

RESUMEN

In this paper, synchronization and encrypted communication transmissions of analog and digital messages in a deterministic small-world network (DSWN) are presented. In the first instance, we use a network with 3 coupled nodes in a nearest-neighbor (NN) topology, then the amount of nodes is increased until reaching a DSWN with 24 nodes. The synchronization and encrypted communication transmissions using a DSWN are presented experimentally by using Chua's chaotic circuit as node, in both analog and digital electronic implementations, where for the continuous version (CV) we use operational amplifiers (OA), and in the discretized version (DV) we use Euler's numerical algorithm implemented in an embedded system by using an Altera/Intel FPGA and external digital-to-analog converters.

11.
J Org Chem ; 87(16): 11000-11006, 2022 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-35921221

RESUMEN

A direct, catalytic, and complementary method to obtain 2-substituted homoallyl sulfonyl amides is described, starting from sulfonyl amides, aldehydes, and allyltrimethylsilane using iron(III) chloride as a sustainable catalyst. The scope of the process and the reactivity in aza-Prins cyclization is evaluated and supported by density functional theory (DFT) studies. Finally, an evaluation of the antiproliferative activity for this family of sulfonyl amides is also included.


Asunto(s)
Amidas , Hierro , Aldehídos , Catálisis , Ciclización
12.
BMC Nephrol ; 23(1): 412, 2022 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-36572867

RESUMEN

BACKGROUND: The current classification for acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria integrates both serum creatinine (SCr) and urine output (UO). Most reports on AKI claim to use KDIGO guidelines but fail to include the UO criterion. It has been shown that patients who had intensive UO monitoring, with or without AKI, had significantly less cumulative fluid volume and fluid overload, reduced vasopressor use, and improved 30-day mortality. We examined whether real-time monitoring of this simple, sensitive, and easy-to-use biomarker in the ICU led to more appropriate intervention by healthcare providers and better outcomes.  METHODS: RenalSense Clarity RMS Consoles were installed in the General ICU at the Hadassah Medical Center, Israel, from December 2019 to November 2020. The Clarity RMS system continuously and electronically monitors UO in real-time. 100 patients were randomly selected from this period as the study group (UOelec) and compared to a matched control group (UOmanual) from the same period two years earlier. To test whether there was an association between oliguric hours and fluid treatment in each group, the correlation was calculated and analyzed for each of the different UO monitoring methods. RESULTS: Therapeutic intervention: The correlation of the sum of all oliguric hours on Day 1 and 2 with the sum of any therapeutic intervention (fluid bolus or furosemide) showed a significant correlation for the study group UOelec (P = 0.017). The matched control group UOmanual showed no such correlation (P = 0.932). Length of Stay (LOS): Median LOS [IQR] in the ICU of UOelec versus UOmanual was 69.46 [44.7, 125.9] hours and 116.5 [62.46, 281.3] hours, respectively (P = 0.0002). CONCLUSIONS: The results of our study strongly suggest that ICU patients had more meaningful and better medical intervention, and improved outcomes, with electronic UO monitoring than with manual monitoring.


Asunto(s)
Lesión Renal Aguda , Riñón , Humanos , Micción , Tiempo de Internación , Creatinina , Electrónica
13.
Emerg Radiol ; 29(5): 879-885, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35729442

RESUMEN

PURPOSE: To analyze the impact of the coronavirus disease (COVID) pandemic on emergency department (ED) computed tomography (CT) utilization. METHODS: A retrospective observational study was conducted assessing seven hospitals' ED imaging volumes between Jan. 6, 2019, and Feb. 27, 2021. Weekly CT utilization is reported as CTs ordered per 100 ED visits. Utilization was ascertained in aggregate and by body area. Interrupted time series analysis was performed to assess significance of utilization change. Prespecified sensitivity analysis was performed for influenza-like or COVID-like illness (ILI/CLI). RESULTS: Weekly ED CT utilization increased from 35.9 CTs per 100 visits (95% confidence interval [95% CI] 35.8-36.1) to 41.8 per 100 visits (95% CI 41.7-42.0) in pre- and post-pandemic periods. Weekly ED CT chest utilization increased immediately following the pandemic declaration (+ 0.52 chest CTs per 100 ED visits, 95% CI 0.01-1.03, p < 0.05) and compared to pre-pandemic period (+ 0.02 per 100 ED visits, 95% CI 0.02-0.05, p < 0.02). For both CT abdomen/pelvis and CT head, there was neither an immediate effect (+ 0.34 CT-AP per 100 ED visits, 95% CI - 0.74 to 1.44, p = 0.89; - 0.42 CT-H per 100 ED visits, 95% CI - 1.53 to 0.70, p = 0.46) nor a change in weekly CT utilization (+ 0.03 CT-AP per 100 ED visits, 95% CI - 0.01 to 0.05, p = 0.09; + 0.03 CT-H per 100 ED visits, 95% CI - 0.01 to 0.06, p = 0.10).  CONCLUSION: These data may help formulate future strategies for resource utilization and imaging operations as we envision a future with COVID and other federal mandates affecting imaging utilization and appropriateness.


Asunto(s)
COVID-19 , Pandemias , Servicio de Urgencia en Hospital , Cabeza , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
14.
Medicina (Kaunas) ; 58(10)2022 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-36295503

RESUMEN

Orthodontic treatment could lead to undesirable effects such as external apical root resorption (EARR). Moreover, trauma to both the face and teeth can predispose to EARR. On the other hand, the practice of combat sports results in increased maxillofacial injuries. Consequently, our objective was to determine if there is a statistically significant difference in the EARR of the patients undergoing fixed orthodontic treatment who practice combat sports and controls. Our null hypothesis was that there is no difference in the EARR between patients undergoing orthodontic treatment who practice combat sports and the patients under the same treatment that do not practice combat sports. An observational, descriptive, and prospective case-control pilot study was designed. The exposed group consisted of patients that practice combat sports. Whereas the control group was conformed of patients that do not practice combat sports without a previous history of facial trauma and without face trauma during the orthodontic treatment. EARR of the maxillary and mandibular anterior teeth was measured using cone-beam computed tomography (CBCT). The CBCT scans were obtained from all patients prior to the beginning of the orthodontic treatment and 1 year later. At the end of the follow-up for the maxillary right central and lateral incisors of the exposed group, the EARR was significantly higher than the homologous teeth of the control group (p < 0.05). As a consequence, the patients treated orthodontically who practice combat sports could be more susceptible to EARR.


Asunto(s)
Resorción Radicular , Humanos , Resorción Radicular/etiología , Proyectos Piloto , Incisivo , Maxilar , Estudios de Casos y Controles
15.
Mol Syst Biol ; 16(12): e9667, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33346944

RESUMEN

Most of our current knowledge on plant molecular biology is based on experiments in controlled laboratory environments. However, translating this knowledge from the laboratory to the field is often not straightforward, in part because field growth conditions are very different from laboratory conditions. Here, we test a new experimental design to unravel the molecular wiring of plants and study gene-phenotype relationships directly in the field. We molecularly profiled a set of individual maize plants of the same inbred background grown in the same field and used the resulting data to predict the phenotypes of individual plants and the function of maize genes. We show that the field transcriptomes of individual plants contain as much information on maize gene function as traditional laboratory-generated transcriptomes of pooled plant samples subject to controlled perturbations. Moreover, we show that field-generated transcriptome and metabolome data can be used to quantitatively predict individual plant phenotypes. Our results show that profiling individual plants in the field is a promising experimental design that could help narrow the lab-field gap.


Asunto(s)
Genes de Plantas , Genómica , Zea mays/genética , Análisis por Conglomerados , Análisis de Datos , Bases de Datos Genéticas , Regulación de la Expresión Génica de las Plantas , Ontología de Genes , Metaboloma/genética , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Estrés Fisiológico/genética , Transcriptoma/genética , Zea mays/crecimiento & desarrollo
16.
Chemistry ; 27(68): 17127-17144, 2021 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-34633707

RESUMEN

Perovskites are interesting oxidation catalysts due to their chemical flexibility enabling the tuning of several properties. In this work, we synthesized LaFe1-x Cox O3 catalysts by co-precipitation and thermal decomposition, characterized them thoroughly and studied their 2-propanol oxidation activity under dry and wet conditions to bridge the knowledge gap between gas and liquid phase reactions. Transient tests showed a highly active, unstable low-temperature (LT) reaction channel in conversion profiles and a stable, less-active high-temperature (HT) channel. Cobalt incorporation had a positive effect on the activity. The effect of water was negative on the LT channel, whereas the HT channel activity was boosted for x>0.15. The boost may originate from a slower deactivation rate of the Co3+ sites under wet conditions and a higher amount of hydroxide species on the surface comparing wet to dry feeds. Water addition resulted in a slower deactivation for Co-rich catalysts and higher activity in the HT channel state.

17.
J Cutan Pathol ; 48(2): 229-236, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32779250

RESUMEN

In the last 30 years, there has been a strong interest in vascular proliferations. Pyogenic granuloma was not only renamed lobular capillary hemangioma, but also the conceptual interpretation was also changed from an overgrowth of granulation tissue to a genuine hemangioma (or benign vascular neoplasm). We describe 19 cases of patients who presented clinically with a vascular lesion, characteristically a pyogenic granuloma or lobular hemangioma, where the histopathological findings led to the pathologic concern for a lymphoma of the skin. These benign lesions with a dense lymphoid infiltrate were further defined on the basis of different vascular and lymphoid immunohistochemical markers as inflammatory lobular hemangiomas. We propose that given the considerable histopathological overlap between acral pseudolymphomatous angiokeratoma, T-cell rich angiomatoid polypoid pseudolymphoma of the skin, and other designations of some of these vascular proliferations with a rich and dense lymphoid infiltrate, they might constitute a spectrum of vascular lesions with varying clinical presentations.


Asunto(s)
Proliferación Celular , Granuloma Piogénico , Hemangioma , Neoplasias Cutáneas , Linfocitos T , Adolescente , Adulto , Anciano , Niño , Femenino , Granuloma Piogénico/metabolismo , Granuloma Piogénico/patología , Hemangioma/irrigación sanguínea , Hemangioma/metabolismo , Hemangioma/patología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/irrigación sanguínea , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Linfocitos T/metabolismo , Linfocitos T/patología
18.
Molecules ; 26(17)2021 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-34500828

RESUMEN

After we identified pGlu-ßGlu-Pro-NH2 as the first functional antagonist of the cholinergic central actions of the thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2), we became interested in finding the receptor-associated mechanism responsible for this antagonism. By utilizing a human TRH receptor (hTRH-R) homology model, we first refined the active binding site within the transmembrane bundle of this receptor to enhance TRH's binding affinity. However, this binding site did not accommodate the TRH antagonist. This directed us to consider a potential allosteric binding site in the extracellular domain (ECD). Searches for ECD binding pockets prompted the remodeling of the extracellular loops and the N-terminus. We found that different trajectories of ECDs produced novel binding cavities that were then systematically probed with TRH, as well as its antagonist. This led us to establish not only a surface-recognition binding site for TRH, but also an allosteric site that exhibited a selective and high-affinity binding for pGlu-ßGlu-Pro-NH2. The allosteric binding of this TRH antagonist is more robust than TRH's binding to its own active site. The findings reported here may shed light on the mechanisms and the multimodal roles by which the ECD of a TRH receptor is involved in agonist and/or antagonist actions.


Asunto(s)
Receptores de Hormona Liberadora de Tirotropina/metabolismo , Sitio Alostérico , Animales , Sitios de Unión , Dominio Catalítico , Humanos
19.
Rev Esp Enferm Dig ; 113(7): 543-544, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33611917

RESUMEN

A 43-year-old female presented to our department with hemoglobin of 3.4 g/dl. She denied gastrointestinal bleeding or weight loss. An upper endoscopy revealed an ulcerative lesion on the greater curvature of the gastric body with two visible clots. Two hemoclips were needed to attain hemostasis, as one of the biopsies of the tumor caused active spurting bleeding. An abdominal computed tomography (CT) demonstrated a well-circumscribed intramural mass arising in the gastric wall, measuring 65 x 50 x 90 mm, with marked internal vascularity and extraluminal component associated. The biopsies identified areas of mature and immature plasmocytes.


Asunto(s)
Plasmacitoma , Adulto , Biopsia , Femenino , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/etiología , Gastroscopía , Humanos , Plasmacitoma/complicaciones , Plasmacitoma/diagnóstico por imagen , Estómago
20.
Rev Esp Enferm Dig ; 113(5): 348-351, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33256418

RESUMEN

Chronic diarrhea is a common symptom seen in the Gastroenterology clinic. Occasionally, the diagnosis is a real challenge as there are multiple entities with unremitting diarrhea as a symptom. Herein, we present a patient affected with intractable diarrhea who was transferred to our department. After many laboratory, endoscopy and radiological tests, she was diagnosed with autoimmune enteropathy (AE) and achieved clinical remission with corticosteroids and azathioprine.


Asunto(s)
Poliendocrinopatías Autoinmunes , Azatioprina/uso terapéutico , Diarrea/etiología , Femenino , Humanos , Poliendocrinopatías Autoinmunes/complicaciones , Poliendocrinopatías Autoinmunes/diagnóstico
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