Antepartum eclampsia <34 weeks case series: advisable to postpone delivery to administer corticosteroids for fetal pulmonary benefit?

OBJECTIVE: To determine if postponement of delivery to administer fetal lung maturation corticosteroids (PDACs) in mothers with antepartum eclampsia <34 weeks gestation benefits the fetus without compromising the mother. STUDY DESIGN: A case series of 37 maternal-perinatal pairs over a 9-year period with antepartum eclampsia between 24 and 34 weeks gestation from a single tertiary center were reviewed retrospectively. Duration of PDAC, clinical course and maternal-fetal outcomes, including impact of duration of PDAC on neonatal pulmonary function, were recorded for each case. Group assignment was based on length of corticosteroid treatment course before delivery: Group A, 0 to ≤ 24 h, n=28; B, 24 to <48 h, n=5; C, ≥ 48 h, n=4. Data were collected and analyzed by one-way analysis of variance (ANOVA), ANOVA on ranks, χ(2)-test and Fisher's exact tests where appropriate; statistical significance was determined by a P-value <0.05. RESULT: Overall, 37 of 68 eclampsia patients in 1999 to 2007 met inclusion criteria. No adverse maternal or fetal event occurred while delivery was postponed. Immediate neonatal intubation or continuous positive airway pressure was required for 23/28 in A, 4/5 in B and 2/4 in C; room air was sufficient at birth for 5/28 in A, 1/5 in B and 2/4 in C. No newborn >33 weeks gestation required INI. Prolonged (that is, >1 day) mechanical ventilation was not required for any infant with a gestational age ≥ 32 weeks or PDAC ≥ 48 h. Two of three neonatal deaths in group A were attributed to pulmonary insufficiency. CONCLUSION: PDAC for antepartum preterm eclampsia, especially ≤ 32 weeks gestation, appears to offer notable fetal pulmonary benefit without significantly increasing maternal or fetal risk.

Adenovirus-mediated overexpression of catalase attenuates oxLDL-induced apoptosis in human aortic endothelial cells via AP-1 and C-Jun N-terminal kinase/extracellular signal-regulated kinase mitogen-activated protein kinase pathways.

In a variety of vascular disorders, endothelial cells (ECs) are exposed to high levels of reactive oxygen species (ROS) generated intercellularly. Recently, several anti-oxidants, including catalase, have been suggested to be cytoprotective against the development of atherosclerosis. The object of this study was to investigate whether adenovirus-mediated gene transfer of catalase in ECs can attenuate ROS production and cell apoptosis under oxidized low density lipoprotein (oxLDL) stimulation. Adenovirus-mediated gene transfer of human catalase gene (Ad-Cat) resulted in a high level of catalase overexpression in human arterial EC (HAEC), which manifested a time-dependent increase in cell viability under the exposure of oxLDL and decreased oxLDL-induced apoptosis. Phosphorylation studies of ERK1/2, JNK, and p38, three subgroups of mitogen activator protein kinase demonstrated that catalase overexpression suppressed JNK phosphorylation and increased ERK1/2 phosphorylation. NF-kappaB and AP-1 were induced after the exposure of HAECs to oxLDL. While catalase overexpression was found to inactivate AP-1, it had no effect on NF-kappaB activity. These results provide the evidence that overexpression of catalase in ECs attenuates ROS production and cell apoptosis under oxLDL stimulation. The protective effect is mediated through the downregulation of JNK and the upregulation of ERK1/2 phosphorylation as well as AP-1 inactivation. This observation supports the feasibility of catalase gene transfer to human endothelium to protect against oxidant injury.

High-level and erythroid-specific expression of human glucose-6-phosphate dehydrogenase in transgenic mice.

Human Glc-6-P dehydrogenase (Glc-6-P) cDNA spanning the entire coding region was subcloned into a pSG5 vector that contains an early SV40 promoter, intron II of the rabbit beta-globin gene, and a polyadenylation signal. This expression cassette was then placed downstream of the human beta-globin locus control region and injected into fertilized mouse eggs. Among five transgenic founders that contained intact copies of the construct, one founder expressed human Glc-6-P dehydrogenase enzyme in a high-level and erythroid-specific fashion (5 x higher than endogenous Glc-6-P dehydrogenase activity). When this male founder mated with a normal individual, all the offspring that carried the transgene showed high-level expression of Glc-6-P dehydrogenase activity in erythroid cells. The endogenous mouse Glc-6-P dehydrogenase in all high-expression mice could be competed out by forming a hybrid with human Glc-6-P dehydrogenase. Our results indicate that the locus control region can drive the human Glc-6-P dehydrogenase gene to be specifically expressed in the erythroid cells of transgenic mice. The results described here provide a basis for experiments designed to express human Glc-6-P dehydrogenase in transgenic mice and suggest a suitable approach to producing a mouse model for studying human Glc-6-P dehydrogenase deficiency.

Diverse point mutations result in glucose-6-phosphate dehydrogenase (G6PD) polymorphism in Taiwan.

Glucose-6-PHOSPHATE dehydrogenase (G6PD; EC 1.1.1.49) deficiency is the most common human enzymopathy, affecting more than 200 million people worldwide. Although greater than 400 variants have been described based on clinical and biochemical criteria, little is known about the molecular basis of these G6PD deficiencies. Recently, the gene that encodes human G6PD has been cloned and sequenced, which enables us to examine directly the heterogeneity of G6PD at the DNA level. During the past 10 years, we examined the G6PD activity in 21,271 newborn Chinese infants (11,400 males and 9,871 females) and identified 314 (2.8%) males and 246 (2.5%) females having low G6PD activity. The G6PD gene from 10 randomly selected affected individuals and their relatives was polymerase chain reaction (PCR) amplified, subcloned, and sequenced. Our results indicate that at least four types of mutation are responsible for the G6PD polymorphism in Taiwan. The first type of mutation (487 G----A) was found in an affected Chinese with a G to A change at nucleotide 487, which results in a (163)Gly to Ser substitution. The second type of mutation (493 A----G) is a novel mutation that has not been reported in any other ethnic group and was identified in two affected Chinese. This mutation causes an A to G change at nucleotide position 493, producing an (165)Asn to Asp substitution. Interestingly, the 487 G----A and 493 A----G mutations create Alu I and Ava II recognition sites, respectively, which enabled us to rapidly detect these two mutations by PCR/restriction enzyme (RE) digestion method. The third mutation (1376 G----T) was found in four affected Chinese. This mutation causes a G to T change at nucleotide position 1376 that results in an (459)Arg to Leu substitution. The 1376 G----T mutation seems to be the dominant allele that causes G6PD deficiency in Taiwan. Finally, two affected Chinese were identified as having the fourth mutation (1388 G----A). This mutation causes a G to A change at nucleotide 1388 that produces an (463)Arg to His substitution. Our studies provide the direct proof of the genetic heterogeneity of G6PD deficiency in the Chinese populations of Taiwan and the PCR/RE digestion method is suitable for simultaneous detection of the 487 G----A and 493 A----G mutations.