Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During pregnancy, calcium is continuously transferred directly from the maternal intestine to the fetal bone, a transfer that is mainly induced by the interrelated actions of the calcium-regulating hormones parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D) and calcitonin. It has recently been demonstrated in animals that PTH-related protein (PTHrP) is the fetal equivalent of PTH. Human PTHrP, originally described as a product of a human lung cancer cell line and implicated in the pathogenesis of humoral hypercalcemia of malignancy, is a protein with 141 amino acids, and it has biochemical actions similar to PTH. It is believed that fetal PTHrP is mainly derived from the placenta during early gestation and from the fetal parathyroid glands during further development and that this protein has the role of maintaining the maternal-fetal calcium gradient either alone or in concert with 1,25(OH)2D. With birth, the placental supply of calcium ceases abruptly, stimulating the increase of PTH and 1,25(OH)2D, which are the main regulators of postnatal calcium metabolism. Alterations in the placental calcium (and phosphate) gradient may be caused by maternal hypo- or hypercalcemia and placental insufficiency and may be followed by transient disorders of calcium metabolism in the newborn. Due to abrupt cessation of the calcium and phosphate supply after delivery at a time when mineral demands are the highest, preterm infants are especially prone to hypocalcemia and osteopathy. If bone disease of prematurity is to be prevented, the amounts of calcium and phosphate must be adequate, as demonstrated by laboratory tests, the most important being calcium and phosphate in urine and alkaline phosphatase activity in serum.
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PMID:[Perinatal calcium metabolism. Physiology and pathophysiology]. 143 20

We have taken a basic biologic approach to elucidate the pathophysiology of bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, based on cell/molecular mechanisms of physiologic lung development. Stretch coordinates parathyroid hormone-related protein (PTHrP) signaling between the alveolar type II cell and the mesoderm to coordinately up-regulate key genes for the homeostatic fibroblast phenotype- including peroxisome proliferator activated receptor gamma (PPARgamma), adipocyte differentiation related protein (ADRP), and leptin- and the retrograde stimulation of type II cell surfactant synthesis by leptin. Each of these paracrine interactions requires cell-specific receptors on adjacent cells derived from the mesoderm or endoderm, respectively, to serially up-regulate the signaling pathways between and within each cell-type. It is this functional compartmentation that is key to understanding how specific agonists and antagonists can predictably affect this mechanism of alveolar homeostasis. Using a wide variety of pathophysiologic insults associated with BPD- barotrauma, oxotrauma, and infection, we have found that there are type II cell and/or fibroblast cell/molecular effects generated by these insults, which can lead to the BPD phenotype. We have exploited these cell-specific mechanisms to effectively prevent and treat lung injuries using PPARgamma agonists to sustain this signaling pathway. It is critically important to judiciously select physiologically and developmentally relevant interventions when treating the preterm neonate.
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PMID:Developmental cell/molecular biologic approach to the etiology and treatment of bronchopulmonary dysplasia. 1751 38