ABSTRACT
Inflammatory bowel disease (IBD) is a chronic, repeated intestinal inflammatory disease. Clinically commonly used therapeutic drugs have some disadvantages, such as poor efficacy and many adverse reactions after long-term application. Although new biological therapies such as anti-tumor necrosis factor agents, overcome common adverse reactions, also have problems such as high price, difficult storage, drug resistance and recurrence after application. In recent years, many new therapeutic methods for inflammatory bowel disease have emerged, for example, modulators that inhibit lymphocyte migration (integrin inhibitors and sphingosine 1-phosphate receptor agonists) have been introduced into the clinical treatment of inflammatory bowel disease, inflammatory cytokine inhibitors (interleukin-23 inhibitors, Janus kinase inhibitors, phosphodiesterase inhibitors, etc.) and inhibitors targeting fibrosis and intestinal tissue degradation and remodeling (matrix metalloproteinase inhibitors) are also being evaluated in clinical trials of IBD. Based on the mechanisms of action, this paper intends to outline the current mainstream IBD therapies and some emerging drugs, and briefly introduce their targets to provide reference for IBD drug design and development.
ABSTRACT
<p><b>BACKGROUND</b>Chronic intermittent hypoxia (CIH) has been associated with abnormalities in the liver, which is the most important organ for drug metabolism. This study aimed to investigate the effect of CIH on theophylline metabolism in mouse liver.</p><p><b>METHODS</b>Eight C57BL/6J mice were exposed to CIH for 12 weeks. Eight C57BL/6J mice were exposed to room air as a control group. Serum levels of alanine aminotransferase and aspartate aminotransferase were measured. Liver histology was observed by light and electron microscopy. Total hepatic cytochrome P450 concentration was measured. Hepatocytes were isolated and incubated with 15 mg/ml theophylline for four hours. After incubation, the theophylline concentration in the supernatant was measured and the theophylline metabolism rate was calculated.</p><p><b>RESULTS</b>CIH did not affect the serum transaminase levels. Livers from mice exposed to CIH showed hepatocellular edema, and liver cells had fuzzy rough endoplasmic reticulum under the electron microscope. The theophylline metabolism rate was significantly inhibited by CIH compared with controls; (16.60 ± 2.43)% vs. (21.58 ± 4.52)% (P = 0.02). The total liver cytochrome P450 concentration in the CIH group was significantly lower than in the control group; (0.83 ± 0.08) vs. (1.13 ± 0.21) mol/mg microsomal protein (P = 0.004).</p><p><b>CONCLUSION</b>CIH decreases theophylline metabolism by mouse hepatocytes, which may correlate with the downregulation of cytochrome P450 expression by CIH.</p>
Subject(s)
Animals , Male , Mice , Chronic Disease , Cytochrome P-450 Enzyme System , Physiology , Hepatocytes , Metabolism , Hypoxia , Metabolism , Liver , Metabolism , Mice, Inbred C57BL , Theophylline , MetabolismABSTRACT
<p><b>AIM</b>To assess whether exogenous estradiol has any effect on migration of primordial germ cells (PGCs) in the chick.</p><p><b>METHODS</b>Fertilized eggs were treated with 17beta-estradiol (E(2)) (80 microg/egg) at stage X (day 0 of incubation), stages 8-10 (incubation 30 h) and 13-15 (incubation 55 h). Controls received vehicle (emulsion) only. Changes in PGC number were measured on different days according to developmental stages.</p><p><b>RESULTS</b>In male right gonads, but not in female left gonads, at stages 28-30 (incubation 132 h) significant decreases in the mean number of PGCs aggregating were observed compared with the controls (P < 0.05) while the total PGC number in the right and left gonads at each stage did not change (P > 0.05).</p><p><b>CONCLUSION</b>The present study provides evidence that E(2) has significant effects on the localization of PGCs in male right, but not female left, gonads of chicken embryos at stages 28-30, compared with controls.</p>
Subject(s)
Animals , Chick Embryo , Female , Male , Cell Movement , Estradiol , Pharmacology , Germ Cells , GonadsABSTRACT
Objective To make it clear whether dust storms may produce same acute adverse impacts on community population. Methods 2 primary schools in Baotou City were selected. During the period of dust storm in March of 2004 an investigation among 918 pupils from third to fifth grades and 1 770 parents of them was conducted by questionnaires. Meanwhile the concentrations of PM2.5 were also determined. Results On the day of dust storms developed the concentrations of PM2.5 obviously increased (212.9 ?g/m3)then decreased rapidly(