RESUMEN
A pronounced heterogeneity between hepatocytes in subcellular structure and enzyme activities was discovered more than 50years ago and initiated the idea of metabolic zonation. In the last decades zonation patterns of liver metabolism were extensively investigated for carbohydrate, nitrogen and lipid metabolism. The present review focuses on zonation patterns of the latter. We review recent findings regarding the zonation of fatty acid uptake and oxidation, ketogenesis, triglyceride synthesis and secretion, de novo lipogenesis, as well as bile acid and cholesterol metabolism. In doing so, we expose knowledge gaps and discuss contradictory experimental results, for example on the zonation pattern of fatty acid oxidation and de novo lipogenesis. Thus, possible rewarding directions of further research are identified. Furthermore, recent findings about the regulation of metabolic zonation are summarized, especially regarding the role of hormones, nerve innervation, morphogens, gender differences and the influence of the circadian clock. In the last part of the review, a short collection of models considering hepatic lipid metabolism is provided. We conclude that modeling, despite its proven benefit for understanding of hepatic carbohydrate and ammonia metabolisms, has so far been largely disregarded in the study of lipid metabolism; therefore some possible fields of modeling interest are presented.
Asunto(s)
Ácidos Grasos/metabolismo , Hepatocitos/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Modelos Biológicos , Animales , Hepatocitos/enzimología , Humanos , Hígado/citología , Hígado/enzimologíaRESUMEN
Elevated levels of oxidative DNA lesions have been noted in many tumors and such damage is strongly implicated in the etiology of cancer. The cumulative risk of cancer increases with the fourth power of age and is associated with an accumulation of oxidative DNA damage. Many agents, synthetic or natural, that can inhibit mutation have been depicted as cancer chemopreventive agents. Antimutagenicity of the 3-hydroxy-3-methylgutaryl-CoA (HMG-CoA) reductase inhibitors atorvastatin and lovastatin was studied using the Ames Salmonella typhimurium assay. Directly acting mutagens, sodium azide (NaN(3)) and 4-nitro-o-phenylenediamine (NPDA), were used to induce mutation in Salmonella strains TA98 and TA100. The antimutagenicity of lovastatin and atorvastatin was found to be significant (p < 0.01) and dose-dependent. The percentage inhibition of a 3 mg lovastatin-treated plate was found to be 79.9% and 61.8% against NPDA- and NaN(3)-induced mutation to TA98 and TA100, respectively. Atorvastatin (0.5 mg/plate) inhibited NPDA-and NaN(3)-induced mutation to TA98 and TA100 by 78.6% and 45.5%, respectively. Atorvastatin showed antimutagenic activity at lower concentrations than lovatstatin. The results of the present study regarding the antimutagenic activity of atorvastatin and lovastatin suggested their therapeutic application as cancer chemopreventive agents.
Asunto(s)
Antimutagênicos/farmacología , Carcinoma/tratamiento farmacológico , Ácidos Heptanoicos/farmacología , Lovastatina/farmacología , Pruebas de Mutagenicidad/métodos , Mutágenos , Pirroles/farmacología , Anticarcinógenos/farmacología , Atorvastatina , Línea Celular Tumoral , Daño del ADN , Relación Dosis-Respuesta a Droga , Humanos , Mutagénesis , Mutación , Salmonella/metabolismo , Salmonella typhimurium/metabolismoRESUMEN
A number of health care organizations are currently undergoing major organizational redesign. Despite these efforts, little is known about how these changes are affecting the employees participating in the redesign process. In response to this, a study was undertaken to determine the perceived impact of organizational redesign on nursing staff at 2 acute care hospitals that were undergoing major organizational change. Data were collected through semi-structured focus group interviews conducted on all 3 shifts (days, evenings, and nights). Findings suggest the early redesign period is highly turbulent and difficult for staff. Nurses expressed concern over changes in roles and responsibilities, disruption in work group relationships, loss of resource availability, reduction in quality of care, and alterations in physical and psychological state.
Asunto(s)
Actitud del Personal de Salud , Reestructuración Hospitalaria , Personal de Enfermería en Hospital/organización & administración , Innovación Organizacional , Atención Dirigida al Paciente/organización & administración , Grupos Focales , Humanos , Personal de Enfermería en Hospital/psicología , Cultura Organizacional , Calidad de la Atención de Salud , Estados UnidosRESUMEN
A retrospective case-control study related to falls was conducted at an 1,120-bed acute care tertiary hospital. The case (fall) sample consisted of 102 falls and 236 control (nonfall) charts during a 1-month period. An instrument developed by Hendrich (1988) was modified for use in the study. Demographic data and risk factors were recorded. Descriptive statistics included risk factor percentages for each sample and the corresponding univariate relative risks. Logistic regression was used to develop a multivariate risk factor model with seven risk factors. The significant risk factors were recent history of falls, depression, altered elimination patterns, dizziness or vertigo, primary cancer diagnosis, confusion, and altered mobility. The adjusted relative risks were converted to risk points to be used to assess a patient's level of fall risk. Within the data set, a sensitivity of 77% (79 of 102) and specificity of 72% (169 of 236) were calculated. The model was cross-validated in a 1987 data set with a sensitivity of 83% (59 of 71) and specificity of 66% (106 of 161).