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• Numerical method for convection-diffusion-reaction equations with mixed derivatives. • Semi-discrete finite difference method considered in nonuniform rectangular grid. • Proof of Stability and Second convergence order with respect to a discrete H 1 -norm. • Application of the method for simulating the cell dynamics in a colonic crypt. This paper proposes a finite difference method for a differential-algebraic system that couples an elliptic equation with a convection-diffusion-reaction equation with mixed derivatives. Herein the parabolic equation depends on the gradient of the solution of the elliptic equation. If the numerical approximation for this gradient presents lower accuracy then the numerical approximations for the solution of the parabolic equation can be deteriorated. In order to get a second order approximation for the solution of the parabolic equation, the challenges that we have to face are the construction of the right discretizations of the elliptic and parabolic equations that lead to a second order approximation for the gradient as well as the development of the numerical analysis of the proposed method. The differential system analysed can be used to describe the cell density and pressure dynamics in colonic crypts. Numerical simulations of cell dynamics in a crypt of the human colon during the formation of a micro-adenoma are presented. [ABSTRACT FROM AUTHOR]

Abstract: Background: Probe-based confocal laser endomicroscopy enables microscopic examination of the digestive mucosa. Aims: (1) To identify and validate quantitative endomicroscopic criteria for evaluation of the colonic mucosa and (2) to compare these criteria between healthy and Crohn's disease patients in clinical remission. Methods: Six healthy controls and ten Crohn's disease patients in clinical remission were included in this prospective study. Methylene blue-stained biopsies of the right colon and corresponding endomicroscopic images were analyzed. Major axis, minor axis, and major axis/minor axis ratio of crypt lumens were quantified. Results: Quantitative assessment was performed on 21±4 crypt lumens per patient. Major axis/minor axis ratio values measured with endomicroscopy or methylene blue-stained biopsies were linearly correlated (r =0.63, p =0.01). All macroscopically inflamed mucosa had values of major axis/minor axis ratio higher than the median of controls. Interestingly, 50% (3/6) of Crohn's disease patients with macroscopically normal mucosa had also a higher ratio than pooled controls. Histological analysis showed that 6/7 patients with major axis/minor axis ratio superior to 1.7 had microscopic inflammation. Conclusion: Probe-based confocal laser endomicroscopy allows quantitative analysis of colonic pit structure. Endomicroscopic analysis of major axis/minor axis ratio allows the detection of microscopic residual inflammation with greater accuracy than standard endoscopy in Crohn's disease patients in clinical remission. [Copyright &y& Elsevier]

Abstract: Colorectal cancer is initiated in colonic crypts as a consequence of alterations leading to the disruption of the normal colonic cellular process. We propose a model, which couples a convection-diffusion type equation with a level set equation, for tracking the time evolution of an epithelial cell set, inside a colonic crypt, until it reaches the top of the crypt. The convection-diffusion equation describes the evolution of the density of the cells in the epithelial cell set. The parameters of this equation regulate the geometric and temporal cellular mechanism, and different parameter choices lead to distinct cell behavior. The level set equation tracks the location and shape of the epithelial cell set, inside the crypt, as well as its interface, separating the cell set from the others cells, which reside within the crypt. The interfacial velocity of the epithelial cell set is obtained from the convection-diffusion type equation. Some in silico experiments are described. They are performed in a relative small time, with respect to the real biological evolution. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies from our laboratory demonstrated that 17β-estradiol (E2) rapidly inhibits Cl− secretion in rat and human distal colonic epithelium. The inhibition has been shown to occur via targeting of a basolateral K+ channel identified as the KCNQ1 (KvLQT1) channel. E2 indirectly modulates the channel activity via a cascade of second messengers which are rapidly phosphorylated in response to E2. The anti-secretory mechanism may be the manner by which E2 induces fluid retention in the intestine during periods of high circulating plasma E2. Here we review the sex-dependent and estrous cycle regulation of this novel rapid response to E2. The inhibition of KCNQ1 channel activity and Cl− secretion will be of interest in the future in the investigation of the retentive effects of estrogen in female tissue and also in the study of secretory disorders and drugable targets of the intestine. [Copyright &y& Elsevier]

Mitochondria produce cellular energy via oxidative phosphorylation (OXPHOS), mediated by respiratory chain complexes I to IV and ATP synthase (complex V). Mitochondrial respiratory complexes have been shown to decline with age in several tissues. As the intestinal epithelium is a tissue with a high energy demand, the aim of the present study was to establish whether the expression profile of OXPHOS subunits in the intestinal mucosa changes during the aging process. Biopsies of intestinal mucosa with no evidence of endoscopic or histomorphologic abnormalities, taken from 55 patients (mean age 42 years, age range 4–82 years; 62% female), were divided into four age groups (4–19, 20–39, 40–59, ≥60 years). Sections from different intestinal segments (terminal ileum, ascending colon, and sigmoid colon/rectum) were stained immunohistochemically (IHC) for subunits of OXPHOS complexes I–V and the voltage-dependent anion-selective channel 1 protein (VDAC1, porin), a marker of mitochondrial mass. Scores for IHC staining were determined by multiplication of the staining intensity and the percentage of positive cells. In addition, the numbers of intestinal crypts staining positive, partly positive, and negative were assessed. The average protein expression levels of OXPHOS subunits increased continuously from childhood onward, peaked in persons aged 20 to 59 years, and declined thereafter. This was seen for complexes II to V in the terminal ileum, complexes I to V in the ascending colon, and complexes I to IV in the sigmoid colon/rectum. Across all age groups, no effect of age on expression of the porin subunit VDAC1 was detected. The number of complex I- and IV-negative crypts in different intestinal segments increased with age. The protein expression levels of OXPHOS complexes increases from childhood onward and declines in elderly individuals, while the numbers of crypts with partial or complete loss of expression of complexes I and IV increase continuously with age. These data suggest that the continued reductions in the levels of mitochondrial OXPHOS complexes in crypts might be compensated in adulthood, but that, ultimately, reduced expression levels occur in persons aged 60 years and older. These findings raise two important questions: first, can the process of aging could be delayed through (pharmacological) intervention of mitochondrial pathways, and second, pathophysiologically, are these findings associated with disorders of the intestinal mucosa, e.g. inflammation? • Mitochondria play a role in the aging process in human intestine. • The levels of oxidative phosphorylation complexes are reduced in elderly persons. • Colonic crypts showing loss of expression of certain complexes increase with age. [ABSTRACT FROM AUTHOR]