ABSTRACT
Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1's effects on liver by comparing wild-type controls, heterozygous igf1+/-, and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage.
Subject(s)
Acute-Phase Proteins/metabolism , Gene Expression Regulation , Hepatitis/metabolism , Inflammation Mediators/metabolism , Insulin-Like Growth Factor I/metabolism , Liver/metabolism , Receptors, Somatomedin/metabolism , Acute-Phase Proteins/genetics , Animals , Cadherins/genetics , Cadherins/metabolism , Crosses, Genetic , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Desmosomes/immunology , Desmosomes/metabolism , Desmosomes/pathology , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Gene Expression Profiling , Hepatitis/immunology , Hepatitis/pathology , Hepatitis/prevention & control , Injections, Subcutaneous , Insulin-Like Growth Factor I/administration & dosage , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/therapeutic use , Lipid Peroxidation , Liver/immunology , Liver/pathology , Male , Mice , Mice, Transgenic , Oxidative Stress , Receptors, Somatomedin/genetics , Tight Junction Proteins/genetics , Tight Junction Proteins/metabolismABSTRACT
Outbreaks of acute gastroenteritis are a public health problem. Norovirus is known as the most common cause (50%). In Chile, immediate notification allows surveillance of these events. We describe an acute gastroenteritis outbreak that occurred in Antofagasta region, between March and April 2010. An observational study was conducted to perform the outbreak investigation. Local residents who met case definition were included. Stool samples, epidemiological surveys and environmental samples were requested. The outbreak began approximately on March 8, 2010 and lasted until April 28 with 31,036 reported cases (rate 54 per 1000 inhabitants). The most affected age group was between 25 and 44 years, and diarrhea was the main symptom (97% of cases). We determined the presence of norovirus genogroup II in clinical and environmental samples. This outbreak was caused by consumption of raw vegetables from La Chimba, which were watered and contaminated with treated sewage containing low concentration of free residual chlorine. Subsequently, the outbreak spread from person to person in a poor sanitary environment.
Subject(s)
Caliciviridae Infections/epidemiology , Disease Outbreaks , Gastroenteritis/epidemiology , Norovirus/isolation & purification , Acute Disease , Adolescent , Adult , Caliciviridae Infections/transmission , Child, Preschool , Chile/epidemiology , Feces/virology , Female , Gastroenteritis/virology , Humans , Infant , Male , Middle AgedABSTRACT
Outbreaks of acute gastroenteritis are a public health problem. Norovirus is known as the most common cause (50%). In Chile, immediate notification allows surveillance of these events. We describe an acute gastroenteritis outbreak that occurred in Antofagasta region, between March and April 2010. An observational study was conducted to perform the outbreak investigation. Local residents who met case definition were included. Stool samples, epidemiological surveys and environmental samples were requested. The outbreak began approximately on March 8, 2010 and lasted until April 28 with 31,036 reported cases (rate 54 per 1000 inhabitants). The most affected age group was between 25 and 44 years, and diarrhea was the main symptom (97% of cases). We determined the presence of norovirus genogroup II in clinical and environmental samples. This outbreak was caused by consumption of raw vegetables from La Chimba, which were watered and contaminated with treated sewage containing low concentration of free residual chlorine. Subsequently, the outbreak spread from person to person in a poor sanitary environment.
Antecedentes: Los brotes por gastroenteritis aguda constituyen un problema de salud pública. Se conoce al norovirus como la causa más común (50%). En Chile, la vigilancia de estos eventos, se establece mediante la notificación inmediata. Objetivo: Investigar y caracterizar el brote de gastroenteritis aguda ocurrido en la Región de Antofagasta, durante los meses de marzo y abril de 2010. Método: Se efectuó un estudio observacional descriptivo para realizar la investigación de brote. Se incluyó a residentes de la región que cumplían con la definición de caso. Se solicitó muestras de deposición, encuesta epidemiológica y muestras ambientales. Resultados: Se estimó que el brote comenzó el 8 de marzo de 2010 y duró hasta el 28 de abril del mismo año; se notificaron 31. 036 casos (tasa 54 por 1.000 habitantes). El grupo de 25 y 44 años de edad fue el más afectado y la diarrea fue el síntoma predominante (97% de los casos). Se determinó la presencia de norovirus genogrupo II en muestras clínicas y ambientales. Conclusiones: El brote se originó por el consumo crudo de hortalizas que provenían del sector La Chimba, las que fueron regadas y contaminadas con agua servida tratada que contenía baja concentración de cloro libre residual y posteriormente se propagó por transmisión persona-persona, en un ambiente sanitario deficiente.