RESUMO
Aging in Caenorhabditis elegans is controlled, in part, by the insulin-like signaling and heat shock response pathways. Following thermal stress, expression levels of small heat shock protein-16.2 show a spatial patterning across the 20 intestinal cells that reside along the length of the worm. Here, we present a hypothesized mechanism that could lead to this patterned response and develop a mathematical model of this system to test our hypothesis. We propose that the patterned expression of heat shock protein is caused by a diffusion-driven instability within the pseudocoelom, or fluid-filled cavity, that borders the intestinal cells in C. elegans. This instability is due to the interactions between two classes of insulin-like peptides that serve antagonistic roles. We examine output from the developed model and compare it to experimental data on heat shock protein expression. Given biologically bounded parameters, the model presented is capable of producing patterns similar to what is observed experimentally and provides a first step in mathematically modeling aging-related mechanisms in C. elegans.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de Choque Térmico/metabolismo , Longevidade/fisiologia , Modelos Biológicos , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/antagonistas & inibidores , Proteínas de Caenorhabditis elegans/genética , Simulação por Computador , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Resposta ao Choque Térmico/genética , Resposta ao Choque Térmico/fisiologia , Interações Hidrofóbicas e Hidrofílicas , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Longevidade/genética , Conceitos Matemáticos , Hormônios Peptídicos/química , Hormônios Peptídicos/genética , Hormônios Peptídicos/metabolismo , Receptor de Insulina/antagonistas & inibidores , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Transdução de SinaisRESUMO
A retrospective chart review of consultations performed by a clinical pharmacist practicing in an adult psychiatric hospital was conducted. Data during the first 12 months of the service were collected from consultation reports, progress notes, physician's orders, laboratory data, and discharge summaries. Twenty-nine consultations were performed, resulting in a total of 135 recommendations. Of those, 125 were assessed and categorized. Of the recommendations, 113 (90.4%) were medication related and 12 (9.6%) were non-medication related. From the 125 recommendations, 99 (79.2%) were implemented and 26 (20.8%) were not. Particular categories of recommendations were also analyzed and had individual implementation rates ranging from 33.3% to 100%. Clinical pharmacists have previously documented their positive impact on patient care in a variety of settings, including psychopharmacy. The majority of recommendations made in this study were medication related with an overall implementation rate of 79%. This report illustrates the influence the clinical pharmacist has on the drug therapy of the psychiatric patient.