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PURPOSE: Apical pleuroparenchymal scarring (APPS) is commonly seen on chest computed tomography (CT), though the imaging and clinical features, to the best of our knowledge, have never been studied. The purpose was to understand APPS's typical morphologic appearance and associated clinical features. PATIENTS AND METHODS: A random generator selected 1000 adult patients from all 21516 chest CTs performed at urban outpatient centers from January 1, 2016 to December 31, 2016. Patients with obscuring apical diseases were excluded to eliminate confounding factors. After exclusions, 780 patients (median age: 64 y; interquartile range: 56 to 72 y; 55% males) were included for analysis. Two radiologists evaluated the lung apices of each CT for the extent of abnormality in the axial plane (mild: <5 mm, moderate: 5 to 10 mm, severe: >10 mm), craniocaudal plane (extension halfway to the aortic arch, more than halfway, vs below the arch), the predominant pattern (nodular vs reticular and symmetry), and progression. Cohen kappa coefficient was used to assess radiologists' agreement in scoring. Ordinal logistic regression was used to determine associations of clinical and imaging variables with APPS. RESULTS: APPS was present on 65% (507/780) of chest CTs (54% mild axial; 80% mild craniocaudal). The predominant pattern was nodular and symmetric. Greater age, female sex, lower body mass index, greater height, and white race were associated with more extensive APPS. APPS was not found to be associated with lung cancer in this cohort. CONCLUSION: Classifying APPS by the extent of disease in the axial or craniocaudal planes, in addition to the predominant pattern, enabled statistically significant associations to be determined, which may aid in understanding the pathophysiology of apical scarring and potential associated risks.
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The flexibility of the ATP synthase's ß subunit promotes its role in the ATP synthase rotational mechanism, but its domains stability remains unknown. A reversible thermal unfolding of the isolated ß subunit (Tß) of the ATP synthase from Bacillus thermophilus PS3, tracked through circular dichroism and molecular dynamics, indicated that Tß shape transits from an ellipsoid to a molten globule through an ordered unfolding of its domains, preserving the ß-sheet residual structure at high temperature. We determined that part of the stability origin of Tß is due to a transversal hydrophobic array that crosses the ß-barrel formed at the N-terminal domain and the Rossman fold of the nucleotide-binding domain (NBD), while the helix bundle of the C-terminal domain is the less stable due to the lack of hydrophobic residues, and thus the more flexible to trigger the rotational mechanism of the ATP synthase.
Subject(s)
Hot Temperature , Molecular Dynamics Simulation , Protein Structure, Secondary , Adenosine Triphosphate/chemistry , Circular Dichroism , Protein Folding , Protein DenaturationABSTRACT
OBJECTIVES: To investigate the incidence, risk factors, and outcomes of barotrauma (pneumomediastinum and subcutaneous emphysema) in mechanically ventilated COVID-19 patients. To describe the chest radiography patterns of barotrauma and understand the development in relation to mechanical ventilation and patient mortality. METHODS: We performed a retrospective study of 363 patients with COVID-19 from March 1 to April 8, 2020. Primary outcomes were pneumomediastinum or subcutaneous emphysema with or without pneumothorax, pneumoperitoneum, or pneumoretroperitoneum. The secondary outcomes were length of intubation and death. In patients with pneumomediastinum and/or subcutaneous emphysema, we conducted an imaging review to determine the timeline of barotrauma development. RESULTS: Forty three out of 363 (12%) patients developed barotrauma radiographically. The median time to development of either pneumomediastinum or subcutaneous emphysema was 2 days (IQR 1.0-4.5) after intubation and the median time to pneumothorax was 7 days (IQR 2.0-10.0). The overall incidence of pneumothorax was 28/363 (8%) with an incidence of 17/43 (40%) in the barotrauma cohort and 11/320 (3%) in those without barotrauma (p ≤ 0.001). In total, 257/363 (71%) patients died with an increase in mortality in those with barotrauma 33/43 (77%) vs. 224/320 (70%). When adjusting for covariates, barotrauma was associated with increased odds of death (OR 2.99, 95% CI 1.25-7.17). CONCLUSION: Barotrauma is a frequent complication of mechanically ventilated COVID-19 patients. In comparison to intubated COVID-19 patients without barotrauma, there is a higher rate of pneumothorax and an increased risk of death.
Subject(s)
Barotrauma , COVID-19 , Mediastinal Emphysema , Pneumothorax , Subcutaneous Emphysema , Barotrauma/complications , Barotrauma/etiology , COVID-19/epidemiology , Humans , Incidence , Mediastinal Emphysema/diagnostic imaging , Mediastinal Emphysema/epidemiology , Mediastinal Emphysema/etiology , Pneumothorax/diagnostic imaging , Pneumothorax/epidemiology , Pneumothorax/etiology , Prognosis , Retrospective Studies , Subcutaneous Emphysema/diagnostic imaging , Subcutaneous Emphysema/epidemiology , Subcutaneous Emphysema/etiologyABSTRACT
BACKGROUND: Recent studies have demonstrated a complex interplay between comorbid cardiovascular disease, COVID-19 pathophysiology, and poor clinical outcomes. Coronary artery calcification (CAC) may therefore aid in risk stratification of COVID-19 patients. METHODS: Non-contrast chest CT studies on 180 COVID-19 patients ≥ age 21 admitted from March 1, 2020 to April 27, 2020 were retrospectively reviewed by two radiologists to determine CAC scores. Following feature selection, multivariable logistic regression was utilized to evaluate the relationship between CAC scores and patient outcomes. RESULTS: The presence of any identified CAC was associated with intubation (AOR: 3.6, CI: 1.4-9.6) and mortality (AOR: 3.2, CI: 1.4-7.9). Severe CAC was independently associated with intubation (AOR: 4.0, CI: 1.3-13) and mortality (AOR: 5.1, CI: 1.9-15). A greater CAC score (UOR: 1.2, CI: 1.02-1.3) and number of vessels with calcium (UOR: 1.3, CI: 1.02-1.6) was associated with mortality. Visualized coronary stent or coronary artery bypass graft surgery (CABG) had no statistically significant association with intubation (AOR: 1.9, CI: 0.4-7.7) or death (AOR: 3.4, CI: 1.0-12). CONCLUSION: COVID-19 patients with any CAC were more likely to require intubation and die than those without CAC. Increasing CAC and number of affected arteries was associated with mortality. Severe CAC was associated with higher intubation risk. Prior CABG or stenting had no association with elevated intubation or death.
Subject(s)
COVID-19 , Coronary Artery Disease , Vascular Calcification , Adult , Biomarkers , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Vessels/diagnostic imaging , Humans , Predictive Value of Tests , Retrospective Studies , Risk Factors , SARS-CoV-2 , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiology , Young AdultABSTRACT
BACKGROUND: Chest radiography (CXR) often is performed in the acute setting to help understand the extent of respiratory disease in patients with COVID-19, but a clearly defined role for negative chest radiograph results in assessing patients has not been described. RESEARCH QUESTION: Is portable CXR an effective exclusionary test for future adverse clinical outcomes in patients suspected of having COVID-19? STUDY DESIGN AND METHODS: Charts of consecutive patients suspected of having COVID-19 at five EDs in New York City between March 19, 2020, and April 23, 2020, were reviewed. Patients were categorized based on absence of findings on initial CXR. The primary outcomes were hospital admission, mechanical ventilation, ARDS, and mortality. RESULTS: Three thousand two hundred forty-five adult patients, 474 (14.6%) with negative initial CXR results, were reviewed. Among all patients, negative initial CXR results were associated with a low probability of future adverse clinical outcomes, with negative likelihood ratios of 0.27 (95% CI, 0.23-0.31) for hospital admission, 0.24 (95% CI, 0.16-0.37) for mechanical ventilation, 0.19 (95% CI, 0.09-0.40) for ARDS, and 0.38 (95% CI, 0.29-0.51) for mortality. Among the subset of 955 patients younger than 65 years and with a duration of symptoms of at least 5 days, no patients with negative CXR results died, and the negative likelihood ratios were 0.17 (95% CI, 0.12-0.25) for hospital admission, 0.09 (95% CI, 0.02-0.36) for mechanical ventilation, and 0.09 (95% CI, 0.01-0.64) for ARDS. INTERPRETATION: Initial CXR in adult patients suspected of having COVID-19 is a strong exclusionary test for hospital admission, mechanical ventilation, ARDS, and mortality. The value of CXR as an exclusionary test for adverse clinical outcomes is highest among young adults, patients with few comorbidities, and those with a prolonged duration of symptoms.
Subject(s)
COVID-19 , Hospitalization/statistics & numerical data , Lung/diagnostic imaging , Radiography, Thoracic , Respiration Disorders , Respiration, Artificial/statistics & numerical data , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Male , Middle Aged , New York City/epidemiology , Predictive Value of Tests , Radiography, Thoracic/methods , Radiography, Thoracic/standards , Radiography, Thoracic/statistics & numerical data , Respiration Disorders/diagnosis , Respiration Disorders/etiology , Respiration, Artificial/methods , Retrospective Studies , SARS-CoV-2ABSTRACT
PURPOSE: We describe the presenting characteristics and hospital course of 11 novel coronavirus (COVID-19) patients who developed spontaneous subcutaneous emphysema (SE) with or without pneumomediastinum (SPM) in the absence of prior mechanical ventilation. MATERIALS AND METHODS: A total of 11 non-intubated COVID-19 patients (8 male and 3 female, median age 61 years) developed SE and SPM between March 15 and April 30, 2020 at a multi-center urban health system in New York City. Demographics (age, gender, smoking status, comorbid conditions, and body-mass index), clinical variables (temperature, oxygen saturation, and symptoms), and laboratory values (white blood cell count, C-reactive protein, D-dimer, and peak interleukin-6) were collected. Chest radiography (CXR) and computed tomography (CT) were analyzed for SE, SPM, and pneumothorax by a board-certified cardiothoracic-fellowship trained radiologist. RESULTS: Eleven non-intubated patients developed SE, 36% (4/11) of whom had SE on their initial CXR. Concomitant SPM was apparent in 91% (10/11) of patients, and 45% (5/11) also developed pneumothorax. Patients developed SE on average 13.3 days (SD: 6.3) following symptom onset. No patients reported a history of smoking. The most common comorbidities included hypertension (6/11), diabetes mellitus (5/11), asthma (3/11), dyslipidemia (3/11), and renal disease (2/11). Four (36%) patients expired during hospitalization. CONCLUSION: SE and SPM were observed in a cohort of 11 non-intubated COVID-19 patients without any known cause or history of invasive ventilation. Further investigation is required to elucidate the underlying mechanism in this patient population.
Subject(s)
Coronavirus Infections/complications , Mediastinal Emphysema/etiology , Pneumonia, Viral/complications , Subcutaneous Emphysema/etiology , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Comorbidity , Coronavirus Infections/virology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Male , Mediastinal Emphysema/epidemiology , Middle Aged , Pandemics , Pneumonia, Viral/virology , Pneumothorax/epidemiology , Pneumothorax/etiology , Respiration, Artificial/adverse effects , SARS-CoV-2 , Subcutaneous Emphysema/epidemiology , Tomography, X-Ray Computed/methodsABSTRACT
Background Chest radiography has not been validated for its prognostic utility in evaluating patients with coronavirus disease 2019 (COVID-19). Purpose To analyze the prognostic value of a chest radiograph severity scoring system for younger (nonelderly) patients with COVID-19 at initial presentation to the emergency department (ED); outcomes of interest included hospitalization, intubation, prolonged stay, sepsis, and death. Materials and Methods In this retrospective study, patients between the ages of 21 and 50 years who presented to the ED of an urban multicenter health system from March 10 to March 26, 2020, with COVID-19 confirmation on real-time reverse transcriptase polymerase chain reaction were identified. Each patient's ED chest radiograph was divided into six zones and examined for opacities by two cardiothoracic radiologists, and scores were collated into a total concordant lung zone severity score. Clinical and laboratory variables were collected. Multivariable logistic regression was used to evaluate the relationship between clinical parameters, chest radiograph scores, and patient outcomes. Results The study included 338 patients: 210 men (62%), with median age of 39 years (interquartile range, 31-45 years). After adjustment for demographics and comorbidities, independent predictors of hospital admission (n = 145, 43%) were chest radiograph severity score of 2 or more (odds ratio, 6.2; 95% confidence interval [CI]: 3.5, 11; P < .001) and obesity (odds ratio, 2.4 [95% CI: 1.1, 5.4] or morbid obesity). Among patients who were admitted, a chest radiograph score of 3 or more was an independent predictor of intubation (n = 28) (odds ratio, 4.7; 95% CI: 1.8, 13; P = .002) as was hospital site. No significant difference was found in primary outcomes across race and ethnicity or those with a history of tobacco use, asthma, or diabetes mellitus type II. Conclusion For patients aged 21-50 years with coronavirus disease 2019 presenting to the emergency department, a chest radiograph severity score was predictive of risk for hospital admission and intubation. © RSNA, 2020 Online supplemental material is available for this article.
Subject(s)
Coronavirus Infections , Lung/diagnostic imaging , Pandemics , Pneumonia, Viral , Adult , Betacoronavirus , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Female , Hospitalization/statistics & numerical data , Humans , Intubation, Intratracheal/statistics & numerical data , Lung/pathology , Male , Middle Aged , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Predictive Value of Tests , Prognosis , Radiography, Thoracic , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome , Young AdultABSTRACT
Introducción. El aprendizaje de la asignatura de Oftalmología en el municipio de Guanajay se desarrolla desde el inicio de la universalización de la Enseñanza Superior. Inmersos en el perfeccionamiento de dicha enseñanza se realizaron controles al sistema de evaluación del aprendizaje, lo que conllevó valorar conocimientos y habilidades del estudiante en el proceso docente educativo. Objetivo: Evaluar los resultados docentes en la asignatura de Oftalmología durante 10 cursos académicos. Material y Métodos: Estudio retrospectivo y descriptivo basado en el análisis de 231 tarjetas evaluativas de los estudiantes de 5to. año de Medicina, asignatura de Oftalmología, pertenecientes a la Facultad de Ciencias Médicas de Artemisa, municipios Guanajay-Artemisa, desde septiembre de 2004 hasta julio de 2014. Los datos se procesaron mediante diferentes técnicas de estadística descriptiva. Resultados: Predominaron los estudiantes con buena asistencia a las actividades (63,6 por ciento). Altos porcentajes de estudiantes obtuvieron excelentes puntuaciones en su rendimiento académico, predominaron las evaluaciones de 5 en las diversas actividades. Existió correlación entre las notas del teórico y la asistencia a las actividades docentes. De los 10 cursos, en 9 se obtuvo una media del rendimiento estudiantil por encima de 90 puntos. Conclusiones: En la década estudiada existió de modo estable una buena asistencia a las actividades docentes, la cual se correlacionó con las calificaciones del examen teórico. El rendimiento académico se consideró excelente, dado el predominio de altas calificaciones en el estudiantado(AU)
Introduction: The learning of the ophthalmology subject in the village of Guanajay began to be developed with the advanced studies universalization. Absorbed in the teaching improvement some evaluations of learning system's controls were done and as a result of this, the students' knowledge, skills and habits in the teaching process were valued. Objective: To evaluate the teaching results achieved by the Ophthalmology subject during 10 courses. Material and methods: Retrospective and descriptive study based on 231 evaluation cards of students from the 5th year of the Medicine career, for Ophthalmology subject in the Artemisa's Medical Sciences Faculty from Guanajay and Artemisa villages from September 2004 to July 2014. The analyses were done using a descriptive statistic technique. Results:Students with good assistance to the curricular activities predominated (63,6 percent). A high percentage of students got excellent results in their academic results, being the 5 points evaluation the most usually in diverse activities. There was a correlation between the grades in the theoretical test and the attendance to the teaching-learning activities. Out of the 10 analyzed courses, in 9 there was obtained as an average, the student's performance over the 90 points. Conclusions: There was a stable and good attendance to the curricular activities in the period studied, which was correlated to the grades in the theoretical exam. The academic performance was considered as excellent due to the predominance of high grades in the students(AU)
Subject(s)
Humans , Male , Female , Ophthalmology/education , Educational Measurement/methods , Epidemiology, Descriptive , Retrospective Studies , UniversitiesABSTRACT
Introducción. El aprendizaje de la asignatura de Oftalmología en el municipio de Guanajay se desarrolla desde el inicio de la universalización de la Enseñanza Superior. Inmersos en el perfeccionamiento de dicha enseñanza se realizaron controles al sistema de evaluación del aprendizaje, lo que conllevó valorar conocimientos y habilidades del estudiante en el proceso docente educativo.Objetivo: Evaluar los resultados docentes en la asignatura de Oftalmología durante 10 cursos académicos. Material y Métodos: Estudio retrospectivo y descriptivo basado en el análisis de 231 tarjetas evaluativas de los estudiantes de 5to. año de Medicina, asignatura de Oftalmología, pertenecientes a la Facultad de Ciencias Médicas de Artemisa, municipios Guanajay-Artemisa, desde septiembre de 2004 hasta julio de 2014. Los datos se procesaron mediante diferentes técnicas de estadística descriptiva. Resultados: Predominaron los estudiantes con buena asistencia a las actividades (63,6 por ciento). Altos porcentajes de estudiantes obtuvieron excelentes puntuaciones en su rendimiento académico, predominaron las evaluaciones de 5 en las diversas actividades. Existió correlación entre las notas del teórico y la asistencia a las actividades docentes. De los 10 cursos, en 9 se obtuvo una media del rendimiento estudiantil por encima de 90 puntos. Conclusiones: En la década estudiada existió de modo estable una buena asistencia a las actividades docentes, la cual se correlacionó con las calificaciones del examen teórico. El rendimiento académico se consideró excelente, dado el predominio de altas calificaciones en el estudiantado(AU)
Introduction: The learning of the ophthalmology subject in the village of Guanajay began to be developed with the advanced studies universalization. Absorbed in the teaching improvement some evaluations of learning systems controls were done and as a result of this, the students knowledge, skills and habits in the teaching process were valued. Objective: To evaluate the teaching results achieved by the Ophthalmology subject during 10 courses. Material and methods: Retrospective and descriptive study based on 231 evaluation cards of students from the 5th year of the Medicine career, for Ophthalmology subject in the Artemisas Medical Sciences Faculty from Guanajay and Artemisa villages from September 2004 to July 2014. The analyses were done using a descriptive statistic technique. Results: Students with good assistance to the curricular activities predominated (63,6 percent). A high percentage of students got excellent results in their academic results, being the 5 points evaluation the most usually in diverse activities. There was a correlation between the grades in the theoretical test and the attendance to the teaching-learning activities. Out of the 10 analyzed courses, in 9 there was obtained as an average, the students performance over the 90 points. Conclusions: There was a stable and good attendance to the curricular activities in the period studied, which was correlated to the grades in the theoretical exam. The academic performance was considered as excellent due to the predominance of high grades in the students(AU)
Subject(s)
Humans , Ophthalmology/methods , Educational Measurement/methods , Learning/ethics , Epidemiology, Descriptive , Retrospective StudiesABSTRACT
Fundamento: en los últimos años se ha observado en el municipio Guanajay, provincia Artemisa, un desplazamiento de lugar entre las primeras causas de muerte. La estructura causal, según las diez primeras causas de muerte, se modifica respecto a años anteriores. Objetivo: describir el comportamiento de la mortalidad en el municipio Guanajay durante el año 2013. Métodos: se realizó un estudio descriptivo, transversal, de todas (158) las defunciones ocurridas en el municipio Guanajay durante el año 2013. Se analizaron, además de variables sociodemográficas (edad, sexo, color de la piel) la causa de muerte. Se determinaron las primeras tres causas de defunción en el periodo señalado, extraídas de los certificados emitidos y que se corresponden con lo establecido en la Décima Revisión de la Clasificación Internacional de Enfermedades. Resultados: se observó un predominio del sexo femenino (56,96 %), con una proporción de mujer/ hombre de 1,3/1. Fue el grupo etario de 67 a 83 años el más afectado en ambos sexos. Las tres primeras causas de muerte fueron: neoplasias malignas, infarto agudo del miocardio y enfermedad cerebrovascular. Las tres primeras localizaciones de los tumores malignos, fueron pulmón, colon y próstata. Conclusión: se concluye que las enfermedades crónicas no transmisibles, en específico las tumorales son las que aportaron más fallecidos en el municipio Guanajay en el año 2013, en correspondencia con lo que ocurre en otras regiones del país.
Background: a change in the leading causes of death has been observed in the municipality of Guanajay, Artemisa province, in recent years. The causal structure, considering the ten leading causes of death, has changed compared to previous years. Objective: to describe mortality in the municipality of Guanajay during 2013. Methods: A cross-sectional study of all (158) deaths in Guanajay during 2013 was conducted. In addition to the cause of death, sociodemographic variables (age, sex, skin color) were analyzed. The top three causes of death in the study period were taken from the certificates issued according to the content of the Tenth Revision of the International Classification of Diseases. Results: females (56.96 %) predominated, with a female-to-male ratio of 1.3: 1. The 67-83 age group was the most affected in both sexes. The three leading causes of death were malignant neoplasms, acute myocardial infarction and cerebrovascular disease. The top three locations of tumors were the lungs, colon and prostate. Conclusions: chronic noncommunicable diseases, in particular tumors, caused a higher number of deaths in Guanajay in 2013, which is similar to what happens in other parts of the country.
ABSTRACT
La enseñanza del método clínico para el diagnóstico constituye una demanda de la sociedad, demanda que se expresa en los lineamientos de la política económica y social del país, aprobados en el VI Congreso del Partido Comunista de Cuba; sin embargo existen insuficiencias en su ejecución en la asignatura Ortodoncia de la carrera de Estomatología. Objetivo: Facilitar a los profesores de ortodoncia elementos del método clínico como sustento para la enseñanza-aprendizaje del diagnóstico de anomalías dentomaxilofaciales en la carrera de Estomatología. Desarrollo: A partir de un marco teórico referencial, se ofrecen consideraciones para la enseñanza-aprendizaje del diagnóstico de anomalías dentomaxilofaciales sustentada en el método clínico, como contenido de la asignatura Ortodoncia. Conclusiones: Las consideraciones realizadas permitieron fundamentar desde la teoría, la utilización del método clínico para el perfeccionamiento de la enseñanza-aprendizaje del diagnóstico de anomalías dentomaxilofaciales.(AU)
The teaching of the clinical method for diagnosis is a demand of the society expressed in the Guidelines of the Economic and Social Policy of the Cuban Party and the Revolution; however, there are weaknesses in its performance in the course in the subject orthodontics of the stomatology career. Objective: To provide orthodontic teachers with elements of the clinical method as support for the teaching and learning of the diagnosis of dentofacial anomalies in the career of stomatology. Development: From identifying the shortcomings of the process and a theoretical framework, considerations for the teaching and learning of the diagnosis of dentofacial anomalies are offered supported by the clinical method in education in the work of the subject of orthodontics. Conclusions: The findings made it possible to base from theory, using the clinical method for improving the teaching and learning of the diagnosis of dentofacial anomalies.(AU)
Subject(s)
Humans , Maxillofacial Abnormalities , Tooth Abnormalities , Orthodontics/education , Teaching/methods , Clinical Diagnosis/education , Education, Dental/methodsABSTRACT
UNLABELLED: Argininosuccinate synthase (ASS) is the rate-limiting enzyme in both the urea and the L-citrulline/nitric oxide (NO·) cycles regulating protein catabolism, ammonia levels, and NO· generation. Because a proteomics analysis identified ASS and nitric oxide synthase-2 (NOS2) as coinduced in rat hepatocytes by chronic ethanol consumption, which also occurred in alcoholic liver disease (ALD) and in cirrhosis patients, we hypothesized that ASS could play a role in ethanol binge and chronic ethanol-induced liver damage. To investigate the contribution of ASS to the pathophysiology of ALD, wildtype (WT) and Ass(+/-) mice (Ass(-/-) are lethal due to hyperammonemia) were exposed to an ethanol binge or to chronic ethanol drinking. Compared with WT, Ass(+/-) mice given an ethanol binge exhibited decreased steatosis, lower NOS2 induction, and less 3-nitrotyrosine (3-NT) protein residues, indicating that reducing nitrosative stress by way of the L-citrulline/NO· pathway plays a significant role in preventing liver damage. However, chronic ethanol-treated Ass(+/-) mice displayed enhanced liver injury compared with WT mice. This was due to hyperammonemia, lower phosphorylated AMP-activated protein kinase alpha (pAMPKα) to total AMPKα ratio, decreased sirtuin-1 (Sirt-1) and peroxisomal proliferator-activated receptor coactivator-1α (Pgc1α) messenger RNAs (mRNAs), lower fatty acid ß-oxidation due to down-regulation of carnitine palmitoyl transferase-II (CPT-II), decreased antioxidant defense, and elevated lipid peroxidation end-products in spite of comparable nitrosative stress but likely reduced NOS3. CONCLUSION: Partial Ass ablation protects only in acute ethanol-induced liver injury by decreasing nitrosative stress but not in a more chronic scenario where oxidative stress and impaired fatty acid ß-oxidation are key events.
Subject(s)
Alcohol Drinking/metabolism , Alcoholism/enzymology , Argininosuccinate Synthase/metabolism , Cytochrome P-450 CYP2E1/metabolism , Hepatocytes/metabolism , Liver Diseases, Alcoholic/enzymology , Acute Disease , Animals , Argininosuccinate Synthase/genetics , Chronic Disease , Cytochrome P-450 CYP2E1/genetics , Disease Models, Animal , Down-Regulation , Ethanol , Female , Hepatocytes/physiology , Immunohistochemistry , Lipid Peroxidation/genetics , Liver Diseases, Alcoholic/genetics , Liver Diseases, Alcoholic/pathology , Male , Mice , Nitric Oxide/metabolism , Oxidative Stress/physiology , Random Allocation , Rats , Tyrosine/analogs & derivatives , Tyrosine/metabolismABSTRACT
Se realiza una revisión de los aspectos relacionados con el surgimiento y desarrollo de la bioética, así como los antecedentes, manifestaciones clínicas, etiopatogenia y manejo multifactorial de la esclerosis múltiple. Se discuten los dilemas bioéticos frente a esta patología(AU)