Electronic cigarettes and obstetric outcomes: a prospective observational study.

OBJECTIVE: To compare the obstetric outcomes and socio-demographic factors in electronic cigarette (EC) users with cigarette smokers and non-smokers in pregnancy. DESIGN: Prospective observational cohort study. SETTING: A large urban maternity hospital delivering almost 8500 infants per year. POPULATION: Pregnant women attending for antenatal care. METHODS: Electronic cigarette users at time of booking history were prospectively identified. Maternal and neonatal outcomes were compared with those of pregnant smokers and non-smokers. Multiple logistic regression analysis was performed to estimate the association between the explanatory variables and birthweight. MAIN OUTCOMES MEASURES: Infant birthweight, gestation at delivery, incidence of low birthweight. RESULTS: A total of 218 women with exclusive EC use and 195 women with dual use of both cigarettes and EC, had a live birth during the study period. EC users were of higher socio-economic status than smokers. Infants born to EC users had a mean birthweight of 3470 g (± 555 g), which was similar to that of non-smokers (3471 ± 504 g, P = 0.97) and significantly greater than that of smokers (3166 ± 502 g, P < 0.001). The mean birth centile of EC users was similar to non-smokers (51st centile versus 47th centile, P = 0.28) and significantly greater than that of smokers (27th centile, P < 0.001). Dual users had a mean birthweight and birth centile similar to that of smokers. CONCLUSION: The birthweight of infants born to EC users is similar to that of non-smokers, and significantly greater than cigarette smokers. Dual users of both cigarettes and EC have a birthweight similar to that of smokers. TWEETABLE EXTRACT: Birthweight of infants born to electronic cigarette users appears to be similar to that of non-smokers.

No evidence for lipid peroxidation in severe preeclampsia.

OBJECTIVE: This study was undertaken to address the role of oxidative stress in preeclampsia. STUDY DESIGN: We measured urinary 8,12-iso-iPF(2alpha)-VI, a chemically stable, free-radical catalyzed product, in a case control study of severe preeclampsia nested within the trial of Calcium for Preeclampsia Prevention. Cases included 29 women who developed severe preeclampsia and from whom urine had been obtained 10 to 20 weeks before the diagnosis of preeclampsia, 3 to 9 weeks before, and 1 day before through delivery. Controls did not develop hypertension or proteinuria and were matched to cases by center, gestational age at each of 3 corresponding urine collections, and date of enrollment. RESULTS: Urinary 8,12-iso -iPF(2alpha)-VI did not differ significantly between cases and controls before or at diagnosis of preeclampsia, nor did it vary with gestational age. CONCLUSIONS: These results call into question the importance of oxidative stress in the disease and the biochemical rationale for clinical trials of antioxidants to prevent and treat preeclampsia.

Reduced fetal exposure to aspirin using a novel controlled-release preparation in normotensive and hypertensive pregnancies.

OBJECTIVES: To examine the fetal effects of a novel controlled-release, low dose aspirin preparation in normal and hypertensive pregnancies. DESIGN: Random double-blind study. Participants assigned to receive conventional formulation aspirin (75 mg), controlled-release low dose aspirin (75 mg), or a matching placebo. SETTING: National Maternity Hospital, Dublin. PARTICIPANTS: Eighteen women with an uncomplicated pregnancy and 18 women with preeclampsia. MAIN OUTCOME MEASURES: Urine was analysed for metabolites of thromboxane and prostacyclin by gas chromatography, mass spectrometry. Serum thromboxane B2 was determined in maternal and cord blood. RESULTS: Both aspirin preparations reduced maternal serum thromboxane B2 by 95% and induced similar reductions in the urinary 11-dehydro-thromboxane B2, a major metabolite of thromboxane A2 in vivo. In contrast, neither preparation altered urinary 2,3-dinor-6-keto PGF1alpha, the major metabolite of prostacyclin. Despite their similar effects in the mothers, the two aspirin preparations differed in their effects on the fetus. While both suppressed cord fetal thromboxane B2, this was significantly (P < 0.005) less for the controlled-release preparation (210+/-42 ng/ml for placebo vs 109+/-22 ng/ml for controlled-release aspirin and 44+/-9 ng/ml for regular oral aspirin). CONCLUSIONS: At equivalent maternal suppression of serum thromboxane B2, a controlled aspirin release preparation results in lower fetal exposure than regular oral aspirin.

Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila.

Genetic analyses have raised the possibility of interactions between the gene products of the neurogenic loci Notch and Delta, each of which encodes a transmembrane protein with EGF homology. To examine the possibility of intermolecular association between the products of these two genes, we studied the effects of their expression on aggregation in Drosophila S2 cells. We find that Notch-expressing cells form mixed aggregates specifically with cells that express Delta and that this process is calcium dependent. In addition, we show that Notch and Delta can associate within the membrane of a single cell, and further, that they form detergent-soluble intermolecular complexes. Our analyses suggest that Notch and Delta proteins interact at the cell surface via their extracellular domains.

Interacting genes that affect microtubule function in Drosophila melanogaster: two classes of mutation revert the failure to complement between haync2 and mutations in tubulin genes.

The recessive male sterile mutation haync2 of Drosophila melanogaster fails to complement certain beta 2-tubulin and alpha-tubulin mutations, suggesting that the haywire product plays a role in microtubule function, perhaps as a structural component of microtubules. The genetic interaction appears to require the presence of the aberrant product encoded by haync2, which may act as a structural poison. Based on this observation, we have isolated ten new mutations that revert the failure to complement between haync2 and B2tn. The revertants tested behaved as intragenic mutations of hay in recombination tests, and fell into two phenotypic classes, suggesting two functional domains of the hay gene product. Some revertants were hemizygous viable and less severe than haync2 in their recessive phenotype. These mutations might revert the poison by restoring the aberrant product encoded by the haync2 allele to more wild-type function. Most of the revertants were recessive lethal mutations, indicating that the hay gene product is essential for viability. These more extreme mutations could revert the poison by destroying the ability of the aberrant haywirenc2 product to interact structurally with microtubules. Flies heterozygous for the original haync2 allele and an extreme revertant show defects in both the structure and the function of the male meiotic spindle.

Temporal and spatial pattern of differences in microtubule behaviour during Drosophila embryogenesis revealed by distribution of a tubulin isoform.

Immunofluorescence staining of Drosophila embryos with a monoclonal antibody specific for acetylated alpha-tubulin has revealed that acetylated and nonacetylated alpha-tubulin isoforms have different patterns of distribution during early development. Acetylated alpha-tubulin was not detected in either interphase or mitotic spindle microtubules during the rapid early cleavage or syncytial blastoderm divisions. Acetylated alpha-tubulin was first observed as interphase lengthened at the end of syncytial blastoderm, and at cycle 14 was localized to a ring of structures clustered around the interphase nuclei. These structures probably represent a set of stable microtubules involved in nuclear elongation. Absence of detectable acetylated alpha-tubulin prior to cellular blastoderm seems to be due to rapid turnover of microtubule arrays rather than to lack of the enzyme required for modification, since acetylated alpha-tubulin appeared in early embryos when micro-tubules were stabilized by taxol treatment or anoxia. Because acetylated alpha-tubulin seems to be characteristic of stable microtubule arrays, the appearance of the antigen at cycle 14 represents a fundamental change in microtubule behaviour in the somatic cells of the embryo. Acetylated alpha-tubulin was not detected in pole cells during the blastoderm or early gastrula stages, indicating that acetylation of alpha-tubulin is not merely a consequence of cellularization. After the onset of gastrulation, interphase microtubule arrays in most cell types contain acetylated alpha-tubulin. However, cells in mitosis lack antibody staining. The resulting unstained patches reveal the stereotyped spatial pattern of cell division during gastrulation. Although the cells that give rise to the amnioserosa have acetylated alpha-tubulin in their interphase arrays at early gastrulation, by germ band elongation these large, plastic cells completely lack staining with anti-acetylated alpha-tubulin. In contrast, differentiated cell types such as neurones, which have arrays of stable axonal microtubules, stain brightly with the specific antibody. Although acetylated and nonacetylated alpha-tubulin are present in roughly equal amounts by the late stages of embryogenesis, acetylated alpha-tubulin is partitioned into the pellet during centrifugation of extracts of embryos homogenized at 4 degrees C.

Interacting genes that affect microtubule function: the nc2 allele of the haywire locus fails to complement mutations in the testis-specific beta-tubulin gene of Drosophila.

A mutation that fails to complement certain alleles of the testis-specific beta 2-tubulin gene (B2t) of Drosophila melanogaster maps to a separate locus, haywire, located at 3-34.4 map units in polytene region 67E3-F3. Second-site non-complementing mutations such as haync2 and B2t alleles could identify genes that encode products that participate in the same functions or that interact in the same structure. Consistent with a structural interaction between the hay gene product and beta 2-tubulin, the genetic interaction between haync2 and B2t requires the presence of the mutant hay gene product; a deficiency for the hay region complements the same alleles of B2t that haync2 fails to complement. haync2 is a recessive male sterile mutation in a genetic background that is wild type at the B2t locus. Homozygous males have defects in meiosis, flagellar elongation and nuclear shaping, the three major microtubule-based processes in which the testis-specific beta 2-tubulin participates. The haync2 allele also has effects outside of spermatogenesis. It is a temperature-sensitive semilethal mutation, and homozygous haync2 females have reduced fertility. These phenotypes are consistent with a role for the haywire gene product in general microtubule function. Analysis of second-site non-complementing mutations such as haync2 offers a genetic tool for analysis of interacting proteins in complex assemblies.