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1.
Front Cell Infect Microbiol ; 11: 598875, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33791232

RESUMEN

In the last year, the advent of the COVID-19 pandemic brought a new consideration for the multidisciplinary sciences. The unknown mechanisms of infection used by SARS-CoV-2 and the absence of effective antiviral pharmacological therapy, diagnosis methods, and vaccines evoked scientific efforts on the COVID-19 outcome. In general, COVID-19 clinical features are a result of local and systemic inflammatory processes that are enhanced by some preexistent comorbidities, such as diabetes, obesity, cardiovascular, and pulmonary diseases, and biological factors, like gender and age. However, the discrepancies in COVID-19 clinical signs observed among those patients lead to investigations about the critical factors that deeply influence disease severity and death. Herein, we present the viral infection mechanisms and its consequences after blocking the angiotensin-converting enzyme 2 (ACE2) axis in different tissues and the progression of inflammatory and immunological reactions, especially the influence of genetic features on those differential clinical responses. Furthermore, we discuss the role of genotype as an essential indicator of COVID-19 susceptibility, considering the expression profiles, polymorphisms, gene identification, and epigenetic modifications of viral entry factors and their recognition, as well as the infection effects on cell signaling molecule expression, which amplifies disease severity.


Asunto(s)
/metabolismo , Sistema Renina-Angiotensina/fisiología , Glicoproteína de la Espiga del Coronavirus/metabolismo , /genética , Antivirales/farmacología , Citocinas/sangre , Citocinas/inmunología , Humanos , Factores de Riesgo , Glicoproteína de la Espiga del Coronavirus/genética
2.
Science ; 372(6537)2021 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-33795432

RESUMEN

Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)-mediated apoptosis, angiopoietin-1 receptor (Tie2)-mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc-angiotensin-converting enzyme 2 (ACE2) fusion proteins.


Asunto(s)
Anticuerpos/química , Anticuerpos/inmunología , Nanoestructuras , Ingeniería de Proteínas , Transducción de Señal , Angiopoyetinas/química , Angiopoyetinas/inmunología , Angiopoyetinas/metabolismo , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/química , Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , Antígenos CD40/química , Antígenos CD40/inmunología , Antígenos CD40/metabolismo , Línea Celular Tumoral , Proliferación Celular , Simulación por Computador , Genes Sintéticos , Humanos , Fragmentos Fc de Inmunoglobulinas/química , Activación de Linfocitos , Modelos Moleculares , Unión Proteica , Receptor TIE-2/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/inmunología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Linfocitos T/inmunología , Linfocitos T/fisiología
3.
Molecules ; 26(7)2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33805024

RESUMEN

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withaniasomnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.


Asunto(s)
Antidepresivos/farmacología , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/fisiología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Animales , Antioxidantes/farmacología , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Técnicas de Inactivación de Genes , Respuesta al Choque Térmico/efectos de los fármacos , Longevidad/efectos de los fármacos , Longevidad/genética , Longevidad/fisiología , Mutación , Presión Osmótica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo
4.
Nutrients ; 13(4)2021 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-33805263

RESUMEN

BACKGROUND: In older people with psychoneurological diseases, COVID-19 infection may be associated with a risk of developing or exacerbating dysphagia. The aim of the present study was to examine the relationship between eating/swallowing function and COVID-19 infection. METHODS: Subjects were 44 inpatients with confirmed COVID-19 infection being treated for schizophrenia in a psychiatric ward. Eating function was assessed using the Food Intake Level Scale (FILS) before and after infection. We also evaluated age, comorbidities, COVID-19 hospital stay, obesity index, weight loss rate, and chlorpromazine equivalent. RESULTS: Subjects had a mean age of 68.86 years. Pre-infection, 20 subjects had a FILS score of 7-9 (presence of eating/swallowing disorder) and 24 subjects had a score of 10 (normal). Eating function after infection resolution showed decreasing FILS score compared to that before infection in 14 subjects (74.14 years). Six subjects (79.3 years) transitioned from oral feeding to parenteral feeding. A ≥ 10% weight loss during infection treatment was significantly associated with decreased eating function and a transition to parenteral feeding. Chlorpromazine equivalents, comorbidities, and number of days of hospitalization showed no associations with decreased eating function. CONCLUSIONS: Preventing malnutrition during treatment for COVID-19 infection is important for improving post-infection life prognosis and maintaining quality of life (QOL).


Asunto(s)
/complicaciones , Trastornos de Deglución/etiología , Trastornos de Alimentación y de la Ingestión de Alimentos/etiología , Esquizofrenia/complicaciones , Pérdida de Peso , Anciano , /psicología , Trastornos de Deglución/fisiopatología , Trastornos de Deglución/psicología , Ingestión de Alimentos/fisiología , Ingestión de Alimentos/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Esquizofrenia/virología
5.
Science ; 372(6537)2021 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-33795429

RESUMEN

Gamma oscillations are thought to coordinate the spike timing of functionally specialized neuronal ensembles across brain regions. To test this hypothesis, we optogenetically perturbed gamma spike timing in the rat medial (MEC) and lateral (LEC) entorhinal cortices and found impairments in spatial and object learning tasks, respectively. MEC and LEC were synchronized with the hippocampal dentate gyrus through high- and low-gamma-frequency rhythms, respectively, and engaged either granule cells or mossy cells and CA3 pyramidal cells in a task-dependent manner. Gamma perturbation disrupted the learning-induced assembly organization of target neurons. Our findings imply that pathway-specific gamma oscillations route task-relevant information between distinct neuronal subpopulations in the entorhinal-hippocampal circuit. We hypothesize that interregional gamma-time-scale spike coordination is a mechanism of neuronal communication.


Asunto(s)
Giro Dentado/fisiología , Corteza Entorrinal/fisiología , Ritmo Gamma , Aprendizaje , Neuronas/fisiología , Aprendizaje Espacial , Potenciales de Acción , Animales , Masculino , Aprendizaje por Laberinto , Recuerdo Mental , Vías Nerviosas/fisiología , Optogenética , Células Piramidales/fisiología , Ratas , Ratas Long-Evans , Navegación Espacial
6.
Science ; 372(6537)2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33795431

RESUMEN

Culture can be defined as all that is learned from others and is repeatedly transmitted in this way, forming traditions that may be inherited by successive generations. This cultural form of inheritance was once thought specific to humans, but research over the past 70 years has instead revealed it to be widespread in nature, permeating the lives of a diversity of animals, including all major classes of vertebrates. Recent studies suggest that culture's reach may extend also to invertebrates-notably, insects. In the present century, the reach of animal culture has been found to extend across many different behavioral domains and to rest on a suite of social learning processes facilitated by a variety of selective biases that enhance the efficiency and adaptiveness of learning. Far-reaching implications, for disciplines from evolutionary biology to anthropology and conservation policies, are increasingly being explored.


Asunto(s)
Conducta Animal , Invertebrados , Conducta Social , Vertebrados , Animales , Evolución Biológica , Mimetismo Biológico , Conducta Consumatoria , Evolución Cultural , Cultura , Herencia , Humanos , Invertebrados/genética , Invertebrados/fisiología , Aprendizaje , Comportamiento del Uso de la Herramienta , Vertebrados/genética , Vertebrados/fisiología , Vocalización Animal
7.
Anticancer Res ; 41(4): 2165-2169, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813428

RESUMEN

BACKGROUND/AIM: In centrally-located lung cancer treatment, it is difficult to attain a sufficient resection margin. It is important to investigate recurrent styles in centrally-located lung cancer patients. PATIENTS AND METHODS: Primary lung cancer located at the hilar area that requires pneumonectomy or sleeve lobectomy is defined as centrally-located lung cancer. Early recurrence was defined as that within 1 year after surgery. RESULTS: This study included 43 centrally-located lung cancer patients. Ten patients underwent pneumonectomy and 33 underwent sleeve lobectomy. Eleven patients experienced early recurrence. Non-squamous cell carcinoma (p=0.012), tumor size>64 mm (p<0.001) and pathological N2 (p=0.012) were significant predictors for early recurrence by univariate analysis. Also, tumor size >64 mm (p=0.006) and pathological N2 (p=0.019) were independent predictors by multivariate analysis. CONCLUSION: Non-squamous cell carcinoma, tumor size and pathological N2 were significant predictors of early recurrence in centrally-located lung cancer. The type of surgical procedure did not affect recurrence development.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Ganglios Linfáticos/patología , Carga Tumoral/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neumonectomía/efectos adversos , Neumonectomía/métodos , Periodo Posoperatorio , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo
8.
Anticancer Res ; 41(4): 2177-2182, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813430

RESUMEN

BACKGROUND/AIM: To investigate the impact of PDZ-binding kinase (PBK) on the clinical outcome of patients with oral squamous cell carcinoma (OSCC) who received radiotherapy. PATIENTS AND METHODS: PBK immunoreactivity of cancer specimens obtained from 179 patients with primary OSCC was analyzed by immunohistochemistry. RESULTS: High PBK expression in tumor cells tended to be associated with advanced N-stage. The 5-year survival rate was greater for patients with high total PBK expression than in those with low PBK expression. After adjustment, high PBK remained associated with a favorable outcome. In subgroups according to tumor stage, the prognostic role was significant in patients with stage III/IV rather than those with stage I/II disease. CONCLUSION: We suggest that PBK expression should be used as an independent prognostic marker for patients with OSCC treated with radiotherapy, especially for those with advanced-stage disease.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/radioterapia , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/radioterapia , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Inmunohistoquímica , Estilo de Vida , Masculino , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/fisiología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Análisis de Supervivencia , Taiwán/epidemiología
9.
BMC Surg ; 21(1): 185, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33827537

RESUMEN

BACKGROUND: Despite the unequivocal role of progressive mobilization in post-surgical patient management, its specific effects and timing, particularly after abdominal surgery, remain debated. This study's aim was to examine the short-term effects of mobilization on oxygenation in hemodynamically stable patients after open surgery for pancreatic cancer. METHODS: A randomized controlled clinical trial was conducted in which patients (n = 83) after open pancreatic surgery were randomized to either the same-day mobilization group (mobilized when hemodynamically stable within four hours after surgery) or the next-day mobilization group (mobilized first time in the morning of the first post-operative day). Mobilization was prescribed and modified based on hemodynamic and subjective responses with the goal of achieving maximal benefit with minimal risk. Blood gas samples were taken three times the evening after surgery; and before and after mobilization on the first post-operative day. Spirometry was conducted pre-operatively and on the first post-operative day. Adverse events and length of stay in postoperative intensive care were also recorded. RESULTS: With three dropouts, 80 patients participated (40 per group). All patients in the same-day mobilization group, minimally sat over the edge of the bed on the day of surgery and all patients (both groups) minimally sat over the edge of the bed the day after surgery. Compared with patients in the next-day mobilization group, patients in the same-day mobilization group required lower FiO2 and had higher SaO2/FiO2 at 1800 h on the day of surgery (p < .05). On the day after surgery, FiO2, SaO2/FiO2, PaO2/FiO2, and alveolar-arterial oxygen gradient, before and after mobilization, were superior in the same-day mobilization group (p < 0.05). No differences were observed between groups in PCO2, pH, spirometry or length stay in postoperative intensive care. CONCLUSIONS: Compared with patients after open pancreatic surgery in the next-day mobilization group, those in the same-day mobilization group, once hemodynamically stable, improved oxygenation to a greater extent after mobilization. Our findings support prescribed progressive mobilization in patients after pancreatic surgery (when hemodynamically stable and titrated to their individual responses and safety considerations), on the same day of surgery to augment oxygenation, potentially helping to reduce complications and hasten functional recovery. TRIAL REGISTRATION: This prospective RCT was carried out at the Sahlgrenska University Hospital, Sweden. The study was approved by the Regional Ethical Review Board in Gothenburg (Registration number: 437-17). TRIAL REGISTRATION: "FoU in Sweden" (Research and Development in Sweden, URL: https://www.researchweb.org/is/vgr ) id: 238701 Registered 13 December 2017 and Clinical Trials (URL:clinicaltrials.gov) NCT03466593. Registered 15 March 2018.


Asunto(s)
Ambulación Precoz , Neoplasias Pancreáticas , Cuidados Posoperatorios , Hemodinámica/fisiología , Humanos , Neoplasias Pancreáticas/rehabilitación , Neoplasias Pancreáticas/cirugía , Estudios Prospectivos , Suecia , Resultado del Tratamiento
12.
Sensors (Basel) ; 21(6)2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33799420

RESUMEN

Parkinson's disease (PD) is a chronic movement disorder that produces a variety of characteristic movement abnormalities. The ubiquity of wrist-worn accelerometry suggests a possible sensor modality for early detection of PD symptoms and subsequent tracking of PD symptom severity. As an initial proof of concept for this technological approach, we analyzed the U.K. Biobank data set, consisting of one week of wrist-worn accelerometry from a population with a PD primary diagnosis and an age-matched healthy control population. Measures of movement dispersion were extracted from automatically segmented gait data, and measures of movement dimensionality were extracted from automatically segmented low-movement data. Using machine learning classifiers applied to one week of data, PD was detected with an area under the curve (AUC) of 0.69 on gait data, AUC = 0.84 on low-movement data, and AUC = 0.85 on a fusion of both activities. It was also found that classification accuracy steadily improved across the one-week data collection, suggesting that higher accuracy could be achievable from a longer data collection. These results suggest the viability of using a low-cost and easy-to-use activity sensor for detecting movement abnormalities due to PD and motivate further research on early PD detection and tracking of PD symptom severity.


Asunto(s)
Acelerometría/instrumentación , Enfermedad de Parkinson/diagnóstico , Temblor/diagnóstico , Dispositivos Electrónicos Vestibles , Acelerometría/métodos , Adulto , Anciano , Bancos de Muestras Biológicas , Marcha/fisiología , Humanos , Aprendizaje Automático , Persona de Mediana Edad , Monitoreo Fisiológico , Enfermedad de Parkinson/fisiopatología , Muñeca
13.
Sensors (Basel) ; 21(6)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805690

RESUMEN

In the midst of the COVID-19 pandemic, Remote Patient Monitoring technologies are highly important for clinicians and researchers. These connected-health technologies enable monitoring of patients and facilitate remote clinical trial research while reducing the potential for the spread of the novel coronavirus. There is a growing requirement for monitoring of the full 24 h spectrum of behaviours with a single research-grade sensor. This research describes a free-living and supervised protocol comparison study of the Verisense inertial measurement unit to assess physical activity and sleep parameters and compares it with the Actiwatch 2 actigraph. Fifteen adults (11 males, 23.4 ± 3.4 years and 4 females, 29 ± 12.6 years) wore both monitors for 2 consecutive days and nights in the free-living study while twelve adults (11 males, 23.4 ± 3.4 years and 1 female, 22 ± 0 years) wore both monitors for the duration of a gym-based supervised protocol study. Agreement of physical activity epoch-by-epoch data with activity classification of sedentary, light and moderate-to-vigorous activity and sleep metrics were evaluated using Spearman's rank-order correlation coefficients and Bland-Altman plots. For all activity, Verisense showed high agreement for both free-living and supervised protocol of r = 0.85 and r = 0.78, respectively. For physical activity classification, Verisense showed high agreement of sedentary activity of r = 0.72 for free-living but low agreement of r = 0.36 for supervised protocol; low agreement of light activity of r = 0.42 for free-living and negligible agreement of r = -0.04 for supervised protocol; and moderate agreement of moderate-to-vigorous activity of r = 0.52 for free-living with low agreement of r = 0.49 for supervised protocol. For sleep metrics, Verisense showed moderate agreement for sleep time and total sleep time of r = 0.66 and 0.54, respectively, but demonstrated high agreement for determination of wake time of r = 0.83. Overall, our results showed moderate-high agreement of Verisense with Actiwatch 2 for assessing epoch-by-epoch physical activity and sleep, but a lack of agreement for activity classifications. Future validation work of Verisense for activity cut-point potentially holds promise for 24 h continuous remote patient monitoring.


Asunto(s)
Acelerometría/instrumentación , Actigrafía/instrumentación , Ejercicio Físico/fisiología , Monitoreo Ambulatorio/instrumentación , Sueño/fisiología , Telemedicina , Telemetría/normas , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio/normas , Pandemias , Reproducibilidad de los Resultados
14.
Epidemiol Psychiatr Sci ; 30: e29, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33820592

RESUMEN

According to the social brain hypothesis, the human brain includes a network designed for the processing of social information. This network includes several brain regions that elaborate social cues, interactions and contexts, i.e. prefrontal paracingulate and parietal cortices, amygdala, temporal lobes and the posterior superior temporal sulcus. While current literature suggests the importance of this network from both a psychological and evolutionary perspective, little is known about its neurobiological bases. Specifically, only a paucity of studies explored the neural underpinnings of constructs that are ascribed to the social brain network functioning, i.e. objective social isolation and perceived loneliness. As such, this review aimed to overview neuroimaging studies that investigated social isolation in healthy subjects. Social isolation correlated with both structural and functional alterations within the social brain network and in other regions that seem to support mentalising and social processes (i.e. hippocampus, insula, ventral striatum and cerebellum). However, results are mixed possibly due to the heterogeneity of methods and study design. Future neuroimaging studies with longitudinal designs are needed to measure the effect of social isolation in experimental v. control groups and to explore its relationship with perceived loneliness, ultimately helping to clarify the neural correlates of the social brain.


Asunto(s)
Encéfalo , Neuroimagen , Aislamiento Social , Encéfalo/fisiología , Humanos
15.
Molecules ; 26(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33807029

RESUMEN

Natural products are gaining more interest recently, much of which focuses on those derived from medicinal plants. The common chicory (Cichorium intybus L.), of the Astraceae family, is a prime example of this trend. It has been proven to be a feasible source of biologically relevant elements (K, Fe, Ca), vitamins (A, B1, B2, C) as well as bioactive compounds (inulin, sesquiterpene lactones, coumarin derivatives, cichoric acid, phenolic acids), which exert potent pro-health effects on the human organism. It displays choleretic and digestion-promoting, as well as appetite-increasing, anti-inflammatory and antibacterial action, all owing to its varied phytochemical composition. Hence, chicory is used most often to treat gastrointestinal disorders. Chicory was among the plants with potential against SARS-CoV-2, too. To this and other ends, roots, herb, flowers and leaves are used. Apart from its phytochemical applications, chicory is also used in gastronomy as a coffee substitute, food or drink additive. The aim of this paper is to present, in the light of the recent literature, the chemical composition and properties of chicory.


Asunto(s)
Achicoria/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antiparasitarios/química , Antiparasitarios/farmacología , Antivirales/química , Antivirales/farmacología , Achicoria/fisiología , Culinaria , Hipersensibilidad a los Alimentos/etiología , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Plantas Medicinales/química
16.
Cardiovasc Diabetol ; 20(1): 75, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33789663

RESUMEN

The 6th Cardiovascular Outcome Trial (CVOT) Summit "Cardiovascular and Renal Outcomes 2020" was the first to be held virtually on October 29-30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA-CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed.The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18-19, 2021 ( http://www.cvot.org ).


Asunto(s)
/epidemiología , Enfermedades Cardiovasculares/epidemiología , Ensayos Clínicos como Asunto/métodos , Congresos como Asunto/tendencias , Insuficiencia Renal Crónica/epidemiología , Informe de Investigación/tendencias , /terapia , Enfermedades Cardiovasculares/terapia , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Humanos , Riñón/efectos de los fármacos , Riñón/fisiología , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Insuficiencia Renal Crónica/terapia , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Resultado del Tratamiento
17.
Circ Res ; 128(7): 1062-1079, 2021 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-33793331

RESUMEN

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associates with a considerable high rate of mortality and represents currently the most important concern in global health. The risk of more severe clinical manifestation of COVID-19 is higher in males and steeply raised with age but also increased by the presence of chronic comorbidities. Among the latter, early reports suggested that arterial hypertension associates with higher susceptibility to SARS-CoV-2 infection, more severe course and increased COVID-19-related deaths. Furthermore, experimental studies suggested that key pathophysiological hypertension mechanisms, such as activation of the renin-angiotensin system (RAS), may play a role in COVID-19. In fact, ACE2 (angiotensin-converting-enzyme 2) is the pivotal receptor for SARS-CoV-2 to enter host cells and provides thus a link between COVID-19 and RAS. It was thus anticipated that drugs modulating the RAS including an upregulation of ACE2 may increase the risk for infection with SARS-CoV-2 and poorer outcomes in COVID-19. Since the use of RAS-blockers, ACE inhibitors or angiotensin receptor blockers, represents the backbone of recommended antihypertensive therapy and intense debate about their use in the COVID-19 pandemic has developed. Currently, a direct role of hypertension, independent of age and other comorbidities, as a risk factor for the SARS-COV-2 infection and COVID-19 outcome, particularly death, has not been established. Similarly, both current experimental and clinical studies do not support an unfavorable effect of RAS-blockers or other classes of first line blood pressure lowering drugs in COVID-19. Here, we review available data on the role of hypertension and its management on COVID-19. Conversely, some aspects as to how the COVID-19 affects hypertension management and impacts on future developments are also briefly discussed. COVID-19 has and continues to proof the critical importance of hypertension research to address questions that are important for global health.


Asunto(s)
/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Antagonistas de Receptores de Angiotensina/metabolismo , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , /metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/metabolismo , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Humanos , Hipertensión/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , Factores de Riesgo
18.
Arch Toxicol ; 95(4): 1179-1226, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33792762

RESUMEN

Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.


Asunto(s)
Compuestos de Organoselenio/farmacología , Compuestos de Organoselenio/toxicidad , Aminoácidos/química , Animales , Azoles , Humanos , Estructura Molecular , Selenio/química , Selenio/fisiología , Selenoproteínas/química , Compuestos de Sulfhidrilo/química
19.
Proc Natl Acad Sci U S A ; 118(16)2021 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-33811184

RESUMEN

Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which the recently emerged SARS-CoV-2 activates or antagonizes these pathways is relatively unknown. We found that SARS-CoV-2 infects patient-derived nasal epithelial cells, present at the initial site of infection; induced pluripotent stem cell-derived alveolar type 2 cells (iAT2), the major cell type infected in the lung; and cardiomyocytes (iCM), consistent with cardiovascular consequences of COVID-19 disease. Robust activation of IFN or OAS-RNase L is not observed in these cell types, whereas PKR activation is evident in iAT2 and iCM. In SARS-CoV-2-infected Calu-3 and A549ACE2 lung-derived cell lines, IFN induction remains relatively weak; however, activation of OAS-RNase L and PKR is observed. This is in contrast to Middle East respiratory syndrome (MERS)-CoV, which effectively inhibits IFN signaling and OAS-RNase L and PKR pathways, but is similar to mutant MERS-CoV lacking innate immune antagonists. Remarkably, OAS-RNase L and PKR are activated in MAVS knockout A549ACE2 cells, demonstrating that SARS-CoV-2 can induce these host antiviral pathways despite minimal IFN production. Moreover, increased replication and cytopathic effect in RNASEL knockout A549ACE2 cells implicates OAS-RNase L in restricting SARS-CoV-2. Finally, while SARS-CoV-2 fails to antagonize these host defense pathways, which contrasts with other coronaviruses, the IFN signaling response is generally weak. These host-virus interactions may contribute to the unique pathogenesis of SARS-CoV-2.


Asunto(s)
Células Epiteliales/inmunología , Células Epiteliales/virología , Inmunidad Innata , Pulmón/patología , Miocitos Cardíacos/inmunología , Miocitos Cardíacos/virología , ARN Bicatenario/metabolismo , /inmunología , Células A549 , Endorribonucleasas/metabolismo , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Nariz/virología , Replicación Viral , eIF-2 Quinasa
20.
Orv Hetil ; 162(16): 615-622, 2021 04 07.
Artículo en Húngaro | MEDLINE | ID: mdl-33830936

RESUMEN

Összefoglaló. A cardiovascularis megbetegedések kialakulását és progresszióját jelentosen befolyásolja az életmód, ezen belül a fizikai aktivitás. A rendszeres testmozgás csökkenti a szív- és érrendszeri kórképek kockázatát, többek között a magas vérnyomásra, a zsíranyagcsere-eltérésekre és az elhízásra gyakorolt kedvezo hatásán keresztül, továbbá független tényezo a cardiovascularis halálozás szempontjából is. Az artériás érfali merevség az elasztikus artériák falát alkotó extracelluláris mátrix degeneratív eltéréseinek következtében alakul ki a különbözo kockázati tényezok hatására. Korábban, különbözo populációkon már igazolták az érfali merevség prediktív értékét a cardiovascularis események kialakulásának tekintetében. A pulzushullám-terjedési sebesség mérése a leggyakrabban alkalmazott módszer az érfali merevség meghatározására. A pulzushullám-terjedési sebesség mérésének hasznát a cardiovascularis kimenetel és élettartam becslésében számos populációs szintu követéses vizsgálat igazolja. Jelen munkánkban áttekintjük a rendszeres fizikai aktivitás, az érfali merevség, az érelmeszesedés és a cardiovascularis események közötti összefüggéseket. Összefoglaljuk az edzésnek és az érfali merevség paramétereinek kapcsolatát egészséges populáción vizsgáló legfontosabb tanulmányok eredményeit. Megállapítjuk, hogy az érfali merevség figyelemre méltó, érdekes biomarker a cardiovascularis kockázat becslése során a rendszeresen sportoló személyek esetén is. Mindezek alapján, tekintve annak prognosztikai hasznát, felmerül a pulzushullám-terjedési sebesség mérésének beillesztése a klinikai döntéshozatali folyamatba mind amator, mind professzionális sportolók esetében. Orv Hetil. 2021; 162(16): 615-622. Summary. The development and progression of cardiovascular disorders is importantly dependent on lifestyle factors, including physical activity. Regular physical activity decreases cardiovascular morbidity by ameliorating risk factors such as hypertension, dyslipidemia and obesity, moreover, also independently affects cardiovascular mortality. Arterial stiffness results from a degenerative process affecting mainly the extracellular matrix of elastic arteries under the effect of risk factors. Previously, the independent predictive value of arterial stiffness for cardiovascular events has been demonstrated in various populations. Pulse wave velocity is the most commonly used method for the assessment of arterial stiffness. The value of measuring pulse wave velocity to predict cardiovascular health outcomes and longevity has been established in several population-based longitudinal studies. In this review, we summarize the main associations between regular physical exercise, arterial stiffness, atherosclerotic burden and incident cardiovascular events. We cite findings from the major studies focusing on the effect of training on arterial stiffness parameters in healthy subjects. We conclude that arterial stiffness is emerging as an interesting biomarker for cardiovascular risk stratification in subjects doing regular physical activity. Therefore, the incorporation of pulse wave velocity measurement into clinical decision-making could be indicated in the case of both amateur and professional athletes, given the prognostic information it provides. Orv Hetil. 2021; 162(16): 615-622.


Asunto(s)
Ejercicio Físico/fisiología , Rigidez Vascular/fisiología , Enfermedades Cardiovasculares , Humanos , Análisis de la Onda del Pulso , Factores de Riesgo
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