The gut mucosa is constantly challenged by a bombardment of foreign antigens and environmental microorganisms. As such, the precise regulation of the intestinal barrier allows the maintenance of mucosal immune homeostasis and prevents the onset of uncontrolled inflammation. In support of this concept, emerging evidence points to defects in components of the epithelial barrier as etiologic factors in the pathogenesis of inflammatory bowel diseases (IBDs). In fact, the integrity of the intestinal barrier relies on different elements, including robust innate immune responses, epithelial paracellular permeability, epithelial cell integrity, as well as the production of mucus. The purpose of this review is to systematically evaluate how alterations in the aforementioned epithelial components can lead to the disruption of intestinal immune homeostasis, and subsequent inflammation. In this regard, the wealth of data from mouse models of intestinal inflammation and human genetics are pivotal in understanding pathogenic pathways, for example, that are initiated from the specific loss of function of a single protein leading to the onset of intestinal disease. On the other hand, several recently proposed therapeutic approaches to treat human IBD are targeted at enhancing different elements of gut barrier function, further supporting a primary role of the epithelium in the pathogenesis of chronic intestinal inflammation and emphasizing the importance of maintaining a healthy and effective intestinal barrier.
The SAMP1/YitFc mouse strain represents a model of Crohn's disease (CD)-like ileitis that is ideal for investigating the pathogenesis of chronic intestinal inflammation. Differently from the vast majority of animal models of colitis, the ileal-specific phenotype characteristic of SAMP1/ YitFc mice occurs spontaneously, without genetic, chemical or immunological manipulation. In addition, SAMP1/YitFc mice possess remarkable similarities to the human condition in regard to disease location, histologic features, incidence of extra-intestinal manifestations, and response to conventional therapies. SAMP1/YitFc mice also display a well-defined time course of a predisease state, and phases of acute and chronic ileitis. As such, the SAMP1/YitFc model is particularly suitable for elucidating pathways that precede the clinical phenotype that may lead to preventive, and therefore more efficacious, intervention with the natural course of disease, or alternatively, for the development of therapeutic strategies directed against chronic, established ileitis. In the following review, we summarize important contributions made by our group and others that uncover potential mechanisms in the pathogenesis of CD using this unique murine model of chronic intestinal inflammation.
Heart disease is the leading cause of death among Filipinos, accounting for 1 out of every 5 deaths in the past year. Each year, 170,000 Filipinos die from cardiovascular diseases, up from 85,000 more than 20 y ago. This paper aims to estimate the risk of developing Heart Attack using Survival Analysis. The data were obtained from the records of Quirino Memorial Medical Center with a total of 447 observations. The data includes the time t (patient's age), gender of the patient, covariates such as lifestyle (smoking and drinking alcohol); health conditions (Hypertension, Diabetes, Highdensity Lipoprotein (HDL) and Low-density Lipoprotein (LDL) level); and family history of Cardiovascular Disease, and the event of interest which is the occurrence of heart attack. The researchers applied two main statistical treatments in examining the data: (1) Cox Regression in formulating a model to estimate the risk of heart attack based on the given covariates; (2) Kaplan-Meier Estimates in calculating the probability of each patient to survive in accordance to their gender depending on the covariates the patients have. Results showed that females have more risks of developing heart attack than males for patients with hypertension, with diabetes, with a family history of CVD, and those who are smoking. However, for patients who are alcoholic, men are more prone to the risk of heart attack than women. The results were obtained with the help of SPSS.
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