Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data from 2543 HIV-infected women were analyzed to correlate antiretroviral therapy (ART) used during pregnancy with maternal and pregnancy outcomes. ART was analyzed according to class of agents used and according to monotherapy versus combination ART containing neither protease inhibitors (PIs) nor nonnucleoside reverse transcriptase inhibitors versus highly active ART. Timing of ART was classified according to early (recorded at or before 25-week gestation study visit) and late (recorded at 32-week gestation or delivery visit) use. Maternal outcomes assessed included hematologic, gastrointestinal, neurologic, renal, and dermatologic complications; gestational diabetes; lactic acidosis; and death. Adverse pregnancy outcomes assessed included hypertensive complications; pre-term labor or rupture of membranes; preterm delivery (PTD); low birth weight; and stillbirth. Logistic regression analyses controlling for multiple covariates revealed ART to be independently associated with few maternal complications: ART use was associated with anemia (odds ratio [OR] = 1.6, 95% confidence interval [CI]: 1.1-2.4), and late use of ART was associated with gestational diabetes (OR = 3.5, 95% CI: 1.2-10.1). Logistic regression analyses revealed an increase in PTD at <37 weeks for 10 women with late use of ART not containing zidovudine (ZDV; OR = 7.9, 95% CI: 1.4-44.6) and a decrease in adverse pregnancy outcomes as follows: late use of ART containing ZDV was associated with decreased risk for stillbirth and PTD at <37 weeks (OR = 0.06, 95% CI: 0.02-0.18; OR = 0.5, 95% CI: 0.3-0.8, respectively), and ART containing nucleoside reverse transcriptase inhibitors but not ZDV during early and late pregnancy was associated with decreased risk for PTD at <32 weeks (OR = 0.3, 95% CI: 0.2-0.7). Benefits of ART continue to outweigh observed risks.
 ...
PMID:Improved obstetric outcomes and few maternal toxicities are associated with antiretroviral therapy, including highly active antiretroviral therapy during pregnancy. 1576 63

Maternal diabetes causes congenital malformations in various organs including the neural tube in fetuses. In this study, we have analyzed the differential gene expression profiling in the cranial neural tube of embryos from diabetic and control mice by using the oligonucleotide microarray. Expression patterns of genes and proteins that are differentially expressed in the cranial neural tube were further examined by the real-time reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunohistochemistry. Proliferation index and apoptosis were examined by BrdU (5-bromo-2-deoxyuridine) labeling and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) assay, respectively. Embryos (E11.5) of diabetic pregnancies displayed distortion in neuroepithelia of the cranial neural tube. Microarray analysis revealed that a total of 390 genes exhibited more than twofold changes in expression level in the cranial neural tube of embryos from diabetic mice. Several genes involving apoptosis, proliferation, migration, and differentiation of neurons in the cranial neural tube were differentially expressed in embryos of diabetic pregnancy. In addition, maternal diabetes perturbed the development of choroid plexus and ventricular systems and reduced the production of proteins such as Ttr and Igf2 in the developing brain, indicating that these changes could impair the survival and proliferation of neuroepithelial cells and neurogenesis in embryos of diabetic mice. It is concluded that altered expression of a variety of genes involved in brain development is associated with cranial neural tube dysmorphogenesis that may subsequently contribute to intellectual impairment of the offspring of a diabetic mother.
 ...
PMID:Global gene expression analysis of cranial neural tubes in embryos of diabetic mice. 1865 3

Lopinavir (LPV) is the preferred HIV protease inhibitor in pregnancy, but it is unknown if gestational diabetes mellitus (GDM) affects its disposition. Hepatic protein expression and plasma protein binding are altered in rodent models of GDM. Because LPV is influenced by hepatic transporters and metabolic enzymes and is highly protein bound, it was hypothesized that streptozotocin-induced GDM would alter its disposition. Maternal and fetal tissues were collected from GDM rats and controls 45 min after LPV injection. In another cohort, fetuses were serially extracted 5 to 60 min after injection. LPV was quantified using liquid chromatography tandem mass spectrometry. Expression of relevant transporters, such as Multidrug resistance protein 1 (Mdr1), and cytochrome P450 3a2 (Cyp3a2), which metabolizes LPV in rodents, was measured in maternal liver via quantitative reverse transcriptase polymerase chain reaction and Western blot analysis. Expression of relevant transporters also was measured in placenta via quantitative reverse transcriptase polymerase chain reaction. Protein binding was determined by ultrafiltration. Relative to controls, we observed dramatically reduced maternal and fetal LPV exposure in GDM. Compared with controls, maternal hepatic Mdr1 and Cyp3a2 were up-regulated, and protein binding was reduced in the GDM group. Increased Mdr1- and Cyp3a2-mediated hepatobiliary clearance, coupled with a larger unbound LPV fraction, is likely to have facilitated hepatic elimination, thereby decreasing maternal and fetal exposure. Not surprisingly, up-regulation of Mdr1 and Cyp3a2's transcriptional regulator, pregnane X receptor, was demonstrated in maternal liver via Western blot analysis. Up-regulation of Mdr1 in placentas isolated from the GDM group likely also contributed to decreased fetal exposure to LPV. This study provides preclinical support for an as yet unreported drug-disease (LPV-GDM) interaction.
 ...
PMID:Mechanisms of reduced maternal and fetal lopinavir exposure in a rat model of gestational diabetes. 2174 99