Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many years have passed since domestic water fluoridation was adopted to reduce the incidence of caries in developed countries; however, since there is an additional dose of fluorides ingested with foods and drinks prepared with such waters, the problem has emerged of possible adverse effects on health associated to them, so that in some countries fluorine integrator selling is allowed only with preventive medical prescription. Owing to the affinity for calcifited tissues, fluorine has a powerful effect on bone cellular order (mediated by growth factors' upregulation system IGF-2, TGF-beta, PDGF, bFGF, EGF, BMP-2 and PTH), on function and length, since it can provoke chronic joints-pain, ligaments-calcification, osteosclerosis. Moreover, sodium-fluoride may cause adverse effects on testicular activity (connected to oxidative-stress depending on increased activity of peroxidases and catalases) due to inhibition of 2 androgenesis-regulator enzymes DELTA(5)b-HSD and 17beta-HSD. Furthermore, insoluble gut formed calcium-fluoride may be responsible for hypocalcemia inducing a secondary hyperparathyroidism with bone matrix resorption, osteoporosis, osteomalacia and, perhaps, lowered level of phosphorus. At encephalic level, then, high doses of fluorine cause the onset of neurological symptoms and of a decreased spontaneous motor activity due to a reduction in the number of nicotinic acetylcholine receptors. Nevertheless, epidemiological studies about fluoride toxicity have established that such oligoelement may be safely used at odontoiatric dosages.
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PMID:[Fluoride toxicity]. 1510 74

Endometriosis is the most common cause of pelvic pain and affects an estimated 5 million women in the US. The biologically active estrogen estradiol (E2) is the best-defined mitogen for the growth and inflammation processes in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Progesterone and progestins may relieve pain by limiting growth and inflammation in endometriosis but a portion of patients with endometriosis and pelvic pain do not respond to treatment with progestins. Moreover, progesterone-induced molecular changes in the eutopic (intrauterine) endometrial tissue of women with endometriosis are either blunted or undetectable. These in vivo observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptors (PRs) and the lack of the PR isoform named progesterone receptor B (PR-B). In normal endometrium, progesterone acts on stromal cells to induce secretion of paracrine factor(s). These unknown factor(s) act on neighboring epithelial cells to induce the expression of the enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD-2), which metabolizes the biologically active estrogen E2 to estrone (E1). In endometriotic tissue, progesterone does not induce epithelial 17beta-HSD-2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate 17beta-HSD-2 may be due to the lack of PR-B and very low levels of progesterone receptor A (PR-A) observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this local mitogen. The cellular and molecular mechanisms underlying progesterone resistance and failure to metabolize E2 in endometriosis are reviewed.
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PMID:Progesterone resistance in endometriosis: link to failure to metabolize estradiol. 1640 81