Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some peculiar aspects of bronchial asthma in women are pointed out and critically examined. The course of asthma is considered during the typical endocrine phases in women (i.e. pregnancy, menstrual cycle and menopause). A worsening is often reported between the 29th and 36th week of pregnancy; the clinical status during pregnancy is attributed to the interaction between the positive effect of cortisol and the antagonism of DOCA, progesterone, aldosterone on the cortisol-glucocorticoid pulmonary receptors. Also the increase of hypotalamic concentration of noradrenaline which inhibits the pituitary-adrenal axis is considered among of the causes of the worsening of symptoms; moreover the increase of progesterone enhances the gastroesophageal reflux which acts as a trigger stimulus and causes bronchospasm. The therapeutic aspects are examined. All the pharmacologic principles are considered regarding the possible harm to the pregnant woman or the fetus. The oldest and well established molecules are considered the most reliable. Bronchial asthma is then examined with regard to menstrual cycle; pre-menstrual asthma is critically reviewed. The Authors conclude that there are neither conclusive data nor a specific therapy. Finally the pathogenesis of perimenopausal asthma is discussed. A possible hyperestrogenism with possible modification of the PGF2/PGE2 rate may be the cause of this syndrome.
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PMID:[Bronchial asthma in women: peculiar aspects]. 268 51

p63 is a member of the p53 protein family that regulates differentiation and morphogenesis in epithelial tissues and is required for the formation of squamous epithelia. Barrett's mucosa is a glandular metaplasia of the squamous epithelium that develops in the lower esophagus in the context of chronic, gastroesophageal reflux and is considered as a precursor for adenocarcinoma. Normal or squamous cancer esophageal cells were exposed to deoxycholic acid (DCA, 50, 100, or 200 microM) and chenodeoxycholic and taurochenodeoxycholic acid at pH 5. p63 and cyclooxygenase-2 (COX-2) expressions were studied by Western blot and RT-PCR. DCA exposure at pH 5 led to a spectacular decrease in the levels of all isoforms of the p63 proteins. This decrease was observed within minutes of exposure, with a synergistic effect between DCA and acid. Within the same time frame, levels of p63 mRNA were relatively unaffected, whereas levels of COX-2, a marker of stress responses often induced in Barrett's mucosa, were increased. Similar results were obtained with chenodeoxycholic acid but not its taurine conjugate at pH 5. Proteasome inhibition by lactacystin or MG-132 partially blocked the decrease in p63, suggesting a posttranslational degradation mechanism. These results show that combined exposure to bile salt and acid downregulates a critical regulator of squamous differentiation, providing a mechanism to explain the replacement of squamous epithelium by a glandular metaplasia upon exposure of the lower esophagus to gastric reflux.
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PMID:Downregulation of p63 upon exposure to bile salts and acid in normal and cancer esophageal cells in culture. 1761 80