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)

Screening women for asymptomatic bacteriuria on the first prenatal visit is a standard of obstetric care. Treating women with positive results decreases the risk of pyelonephritis and possible prematurity. This study uses decision and cost analysis to compare the utility of screening for asymptomatic bacteriuria with not screening. Data are based on published reports and average charges for services. Costs are based on 1988 charges, projected for the expected results of outpatient screening, possible suppressive therapy, and risks of pyelonephritis. Screening is based on the combined sensitivities and specificities of the MacConkey and CLED (cysteine-lactose-electrolyte-deficient agar) panels of the dip-slide culture. Under the baseline assumptions, the risk of pyelonephritis is estimated to be 2 cases per 100 screened women vs 3.5 cases per 100 unscreened women. The anticipated cost of screening 100 women is $9,939, compared with $12,824 for not screening 100 women. Screening is cost saving unless the cost of screening is above $26, the length of hospitalization for pyelonephritis is fewer than 2.2 days, the risk of asymptomatic bacteriuria falls below 2%, the risk of pyelonephritis with asymptomatic bacteriuria falls below 13%, or the efficacy of treatment in preventing pyelonephritis falls below 38%.
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PMID:Screening for asymptomatic bacteriuria in pregnancy. A decision and cost analysis. 210 74

Prematurity has been associated with low glutathione (GSH) concentrations in bronchoalveolar lavage fluid as well as in leukocytes from tracheal aspirates and peripheral blood. To elucidate whether this is caused by deficient GSH synthesis, the expression and activity of gamma-glutamylcysteine synthetase (glutamate-cysteine ligase, GCS, EC 6.3.2.2), the rate-limiting enzyme for GSH synthesis, were measured from fetal, neonatal, and adult human liver, lung, and kidney samples. The highest activity was measured in the liver, in which mRNA expression of the catalytic GCS heavy and the regulatory light subunits, as well as activity, were, on average, similar in the various stages of development. Although GCS light subunit mRNA concentrations in the lung were higher in neonates than in fetuses and adults, enzyme activities were similar. In the adult kidney, mean enzyme activity was somewhat higher than in fetal or neonatal kidney, but this may be accounted for by the variation in the small number of samples. In conclusion, GCS is expressed and active already in the second trimester and thus low GSH concentrations found in preterm neonates appear not to be explained by deficient GSH synthesis. Other factors, such as limited availability of the GSH precursor cysteine or increased GSH consumption, may account for the lower concentrations of GSH found in preterm infants.
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PMID:Expression of gamma-glutamylcysteine synthetase during development. 1067 57

Intestinal failure-associated liver disease develops in 40% to 60% of infants who require long-term total parenteral nutrition (TPN) for intestinal failure and 15% to 40% of adults on home parenteral nutrition. The clinical spectrum includes hepatic steatosis, cholestasis, cholelithiasis, and hepatic fibrosis. Progression to biliary cirrhosis and the development of portal hypertension and liver failure occurs in a minority but is more common in infants and neonates than in adults. The pathogenesis is multifactorial. In infants it is related to prematurity, low birth weight, duration of PN, short bowel syndrome requiring multiple laparotomies, and recurrent sepsis. Other important mechanisms include lack of enteral feeding, which leads to reduced gut hormone secretion; reduction of bile flow and biliary stasis, which leads to the development of cholestasis; and biliary sludge and gallstones, which exacerbate hepatic dysfunction. In adults, IFALD is less common and related to age, length of time on PN, total caloric intake, and lipid or glucose overload. In preterm infants, a deficiency of taurine or cysteine may play a role, whereas in both adults and children, choline deficiency may exacerbate IFALD. Lipid emulsions, choline deficiency, and manganese toxicity are associated with both hepatic steatosis and cholestasis in adults and children. Management strategies for the prevention of intestinal failure-induced liver disease include early enteral feeding, a multidisciplinary approach to the management of parenteral nutrition, and aseptic catheter techniques to reduce sepsis. The addition of choline, taurine, and cysteine to PN solutions may also play a role. Oral administration of ursodeoxycholic acid may improve bile flow and reduce gallbladder stasis. Survival after either isolated small bowel or combined liver and small bowel transplantation is approximately 50% at 5 years, making this an acceptable therapeutic option in adults and children with irreversible liver and intestinal failure.
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PMID:Intestinal failure-associated liver disease: what do we know today? 1647 75

The adequacy range of dietary requirements of specific amino acids in disease states is difficult to determine. In health, several techniques are available allowing rather precise quantification of requirements based on growth of the organism, rises in plasma concentration, or increases in the oxidation of marker amino acids during incremental administration of the amino acid under study. Requirements may not be similar in disease with regard to protein synthesis or with regard to specific functions such as scavenging of reactive oxygen species by compounds including glutathione. Requirements for this purpose can be assessed only when such a function can be measured and related to clinical outcome. There is apparent consensus concerning normal sulfur amino acid (SAA) requirements. WHO recommendations amount to 13 mg/kg per 24 h in healthy adults. This amount is roughly doubled in artificial nutrition regimens. In disease or after trauma, requirements may be altered for methionine, cysteine, and taurine. Although in specific cases of congenital enzyme deficiency, prematurity, or diminished liver function, hypermethionemia or hyperhomocysteinemia may occur, SAA supplementation can be considered safe in amounts exceeding 2-3 times the minimal recommended daily intake. Apart from some very specific indications (e.g., acetaminophen poisoning), the usefulness of SAA supplementation is not yet established. There is a growing body of data pointing out the potential importance of oxidative stress and resulting changes in redox state in numerous diseases including sepsis, chronic inflammation, cancer, AIDS/HIV, and aging. These observations warrant continued attention for the potential role of SAA supplementation. In particular, N-acetylcysteine remains promising for these conditions.
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PMID:Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition. 1670 41

Mutations in the gene coding for ATP-binding cassette protein A3 (ABCA3) are recognized as a genetic cause of lung disease of varying severity. Characterization of a number of mutant ABCA3 proteins has demonstrated that the mutations generally affect intracellular localization or the ability of the protein to hydrolyze ATP. A novel heterozygous mutation that results in the substitution of cysteine for arginine at amino acid 295 in ABCA3 was identified in a premature infant with chronic respiratory insufficiency and abnormal lamellar bodies. Sequencing of DNA performed in study participants demonstrated that this was a mutation and not a common variant. Plasmid vectors containing ABCA3 with the identified novel mutation tagged with green fluorescent protein on the carboxy terminus were generated. The effect of the mutation on protein function was characterized by examining the glycosylation state of the mutant protein in transiently transfected HEK293 cells and by examining ATP hydrolysis activity of the mutant protein with a vanadate-induced nucleotide trapping assay in stably transfected HEK293 cells. The ABCA3 protein containing the R295C mutation undergoes normal glycosylation and intracellular localization but has dramatically reduced ATP hydrolysis activity (12% of wild type). The identification of one copy of this novel mutation in a premature infant with chronic respiratory insufficiency suggests that ABCA3 haploinsufficiency together with lung prematurity may result in more severe, or more prolonged, respiratory failure.
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PMID:Identification and characterization of a novel ABCA3 mutation. 1986 31

Extreme prematurity is a major risk factor for perinatal and neonatal brain injury, and can lead to white matter injury that is a precursor for a number of neurological diseases, including cerebral palsy (CP) and autism. Neuroinflammation, mediated by activated microglia and astrocytes, is implicated in the pathogenesis of neonatal brain injury. Therefore, targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes in models of perinatal white matter injury. In this work, we use a mouse model of ischemia-induced neonatal white matter injury to study the biodistribution of generation 4, hydroxyl-functionalized polyamidoamine dendrimers. Following systemic administration of the Cy5-labeled dendrimer (D-Cy5), we demonstrate dendrimer uptake in cells involved in ischemic injury, and in ongoing inflammation, leading to secondary injury. The sub-acute response to injury is driven by astrocytes. Within five days of injury, microglial proliferation and migration occurs, along with limited differentiation of oligodendrocytes and oligodendrocyte death. From one day to five days after injury, a shift in dendrimer co-localization occurred. Initially, dendrimer predominantly co-localized with astrocytes, with a subsequent shift towards microglia. Co-localization with oligodendrocytes reduced over the same time period, demonstrating a region-specific uptake based on the progression of the injury. We further show that systemic administration of a single dose of dendrimer-N-acetyl cysteine conjugate (D-NAC) at either sub-acute or delayed time points after injury results in sustained attenuation of the 'detrimental' pro-inflammatory response up to 9days after injury, while not impacting the 'favorable' anti-inflammatory response. The D-NAC therapy also led to improvement in myelination, suggesting reduced white matter injury. Demonstration of treatment efficacy at later time points in the postnatal period provides a greater understanding of how microglial activation and chronic inflammation can be targeted to treat neonatal brain injury. Importantly, it may also provide a longer therapeutic window.
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PMID:Systemic dendrimer-drug treatment of ischemia-induced neonatal white matter injury. 2618 52

Preterm birth is a major risk factor for adverse neurological outcomes in ex-preterm children, including motor, cognitive, and behavioral disabilities. N-acetyl-L-cysteine therapy has been used in clinical studies; however, it requires doses that cause significant side effects. In this study, we explore the effect of low dose N-acetyl-L-cysteine therapy, delivered using a targeted, systemic, maternal, dendrimer nanoparticle (DNAC), in a mouse model of intrauterine inflammation. Our results demonstrated that intraperitoneal maternal DNAC administration significantly reduced the preterm birth rate and altered placental immune profile with decreased CD8+ T-cell infiltration. Furthermore, we demonstrated that DNAC improved neurobehavioral outcomes and reduced fetal neuroinflammation and long-term microglial activation in offspring. Our study is the first to provide evidence for the role of CD8+ T-cell in the maternal-fetal interface during inflammation and further support the efficacy of DNAC in preventing preterm birth and prematurity-related outcomes.
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PMID:Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury. 2873 19