Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with bile acid malabsorption, high concentrations of bile acids enter the colon and stimulate Cl(-) and fluid secretion, thereby causing diarrhoea. However, deoxycholic acid (DCA), the predominant colonic bile acid, is normally present at lower concentrations where its role in regulating transport is unclear. Thus, the current study set out to investigate the effects of physiologically relevant DCA concentrations on colonic epithelial secretory function. Cl(-) secretion was measured as changes in short-circuit current across voltage-clamped T(84) cell monolayers. At high concentrations (0.5-1 mM), DCA acutely stimulated Cl(-) secretion but this effect was associated with cell injury, as evidenced by decreased transepithelial resistance (TER) and increased lactate dehydrogenase (LDH) release. In contrast, chronic (24 hrs) exposure to lower DCA concentrations (10-200 microM) inhibited responses to Ca(2+) and cAMP-dependent secretagogues without altering TER, LDH release, or secretagogue-induced increases in intracellular second messengers. Other bile acids - taurodeoxycholic acid, chenodeoxycholic acid and cholic acid - had similar antisecretory effects. DCA (50 microM) rapidly stimulated phosphorylation of the epidermal growth factor receptor (EGFr) and both ERK and p38 MAPKs (mitogen-activated protein kinases). The EGFr inhibitor, AG1478, and the protein synthesis inhibitor, cycloheximide, reversed the antisecretory effects of DCA, while the MAPK inhibitors, PD98059 and SB203580, did not. In summary, our studies suggest that, in contrast to its acute prosecretory effects at pathophysiological concentrations, lower, physiologically relevant, levels of DCA chronically down-regulate colonic epithelial secretory function. On the basis of these data, we propose a novel role for bile acids as physiological regulators of colonic secretory capacity.
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PMID:Physiological concentrations of bile acids down-regulate agonist induced secretion in colonic epithelial cells. 1958 9

Giardia lamblia is one of the most prevalent parasites residing in the duodenum of human and many other mammals throughout the world which is transmitted via ingested cysts through contaminated food or water. The severity of disease may depend on multiple parasite and host factors. Commonly, children and immunologically compromised persons like AIDS patient exhibit severe diarrhea, malabsorption and weight loss, however, there are also some infected people who are asymptomatic or only exhibit mild clinical symptoms and can shed the Giardia cysts in the environment. Although many studies have indicated that the innate immune system is important for Giardia defense, however, whether the innate immune responses such extracellular traps (ETs) could be induced by G. lamblia is still unclear. In recent years, macrophage extracellular traps (METs) have been described as an effective defense mechanism against invading microorganisms. In the present study, the formation of METs triggered by G. lamblia trophozoites was investigated. The formation of METs induced by G. lamblia trophozoites of mouse macrophage was observed with Scanning Electron Microscopy (SEM). The main components DNA, H3 histone and MPO were confirmed by Sytox orange staining, DNase1 digestion, immunofluorescence staining and fluorescence confocal microscopy. Inhibitor assays suggested that G. lamblia trophozoites triggered METs formation through ERK1/2 and p38 MAPK signal pathways and was Store-operated Ca2+ entry (SOCE) dependent. In addition, the process of METs formation triggered by G. lamblia trophozoites was also time and dose-dependent. Furthermore, the production of Reactive Oxygen Species (ROS) in macrophages stimulated with G. lamblia trophozoites significantly increased whereas no significant changes were observed about LDH activity.
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PMID:Mouse macrophages capture and kill Giardia lamblia by means of releasing extracellular trap. 3004 99

Nutrients are absorbed solely by the intestinal villi. Aging of this organ causes malabsorption and associated illnesses, yet its aging mechanisms remain unclear. Here, we show that aging-caused intestinal villus structural and functional decline is regulated by mTORC1, a sensor of nutrients and growth factors, which is highly activated in intestinal stem and progenitor cells in geriatric mice. These aging phenotypes are recapitulated in intestinal stem cell-specific Tsc1 knockout mice. Mechanistically, mTORC1 activation increases protein synthesis of MKK6 and augments activation of the p38 MAPK-p53 pathway, leading to decreases in the number and activity of intestinal stem cells as well as villus size and density. Targeting p38 MAPK or p53 prevents or rescues ISC and villus aging and nutrient absorption defects. These findings reveal that mTORC1 drives aging by augmenting a prominent stress response pathway in gut stem cells and identify p38 MAPK as an anti-aging target downstream of mTORC1.
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PMID:Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway. 3189 47