Smoking in preeclamptic women is associated with higher birthweight for gestational age and lower soluble fms-like tyrosine kinase-1 levels: a nested case control study

<p>Abstract</p> <p>Background</p> <p>Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U-shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers.</p> <p>Methods</p> <p>From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit.</p> <p>Results</p> <p>In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (β = -0.29; p = 0.008, and β = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (β = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054).</p> <p>Conclusions</p> <p>Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti-angiogenic protein sFlt-1.</p

Cholinergic Muscarinic Receptors in Human Fetal Brain: Ontogeny of [3H]Quinuclidinyl Benzilate Binding Sites in Corpus Striatum, Brainstem, and Cerebellum

The ontogeny of muscarinic receptors was studied in human fetal striatum, brainstem, and cerebellum to investigate general principles of synaptogenesis as well as the physiological balance between various chemical synapses during development in a given region of the brain. [3H]Quinuclidinyl benzilate ([-'H]QNB) binding was assayed in total particulate fraction (TPF) from various parts of brain. In the corpus striatum, QNB binding sites are present at 16 weeks of gestation (average concentration 180 fmol/mg protein of TPF), slowly increase up to 24 weeks (average concentration 217 fmol/mg protein), and rapidly increase during the third trimester to 480 fmol/mg protein of TPF. In contrast, dopaminergic receptors exist as two subpopulations. one with low affinity and the other with high affinity up to the 24th week of gestation; all of them acquire the highaffinity characteristic during the third trimester. In brainstem, the muscarinic receptors show maximum concentration by 16 weeks of age (360 fmolimg protein of TPF). Subsequently the muscarinic receptor concentration shows a gradual decline in the brainstem. In cerebellum, except for a slight increase at 24 weeks (average concentration 90 fmol/mg protein of TPF), the receptor concentration remained nearly constant at about 60-70 fmolimg protein of TPF throughout fetal life. This study demonstrates that the ontogeny of muscarinic receptors varies among the different regions, and the patterns observed suggest that receptor formation occurs principally in the third trimester. Also noteworthy is the finding that the QNB binding sites decreased in all regions of the human brain during adult life. Key Words: Cholinergic muscarinic receptors-Quinuclidinyl benzilate-Corpus striaturn-Brainstem-Cerebellum. Ravikumar B. V. and Sastry P. S. Cholinergic muscarinic receptors in human fetal brain: Ontogeny of [3H]quinuclidinyl benzilate binding sites in corpus striatum, brainstem, and cerebellum. J. Neurochem. 45, 1948- 1950 (1985)

Dopamine receptors in human foetal brains:Characterization, regulation and ontogeny of [3H]spiperone binding sites in striatum

Eighteen corpora striata from normal human foetal brains ranging in gestational age from 16 to 40 weeks and five from post natal brains ranging from 23 days to 42 years were analysed for the ontogeny of dopamine receptors using [3H]spiperone as the ligand and 10 mM dopamine hydrochloride was used in blanks. Spiperone binding sites were characterized in a 40-week-old foetal brain to be dopamine receptors by the following criteria: (1) It was localized in a crude mitochondrial pellet that included synaptosomes; (2) binding was saturable at 0.8 nM concentration; (3) dopaminergic antagonists spiperone, haloperidol, pimozide, trifluperazine and chlorpromazine competed for the binding with IC50 values in the range of 0.3–14 nM while agonists—apomorphine and dopamine gave IC50 values of 2.5 and 10 μM, respectively suggesting a D2 type receptor.Epinephrine and norepinephrine inhibited the binding much less efficiently while mianserin at 10 μM and serotonin at 1 mM concentration did not inhibit the binding. Bimolecular association and dissociation rate constants for the reversible binding were 5.7 × 108 M−1 min−1 and 5.0 × 10−2 min−1, respectively. Equilibrium dissociation constant was 87 pM and the KD obtained by saturation binding was 73 pM.During the foetal age 16 to 40 weeks, the receptor concentration remained in the range of 38–60 fmol/mg protein or 570–1080 fmol/g striatum but it increased two-fold postnatally reaching a maximum at 5 years Significantly, at lower foetal ages (16–24 weeks) the [3H]spiperone binding sites exhibited a heterogeneity with a high (KD, 13–85 pM) and a low (KD, 1.2–4.6 nM) affinity component, the former accounting for 13–24% of the total binding sites. This heterogeneity persisted even when sulpiride was used as a displacer. The number of high affinity sites increased from 16 weeks to 24 weeks and after 28 weeks of gestation, all the binding sites showed only a single high affinity.GTP decreased the agonist affinity as observed by dopamine competition of [3H]spiperone binding in 20-week-old foetal striata and at all subsequent ages. GTP increased IC50 values of dopamine 2 to 4.5 fold and Hill coefficients were also increased becoming closer to one suggesting that the dopamine receptor was susceptible to regulation from foetal life onwards

Design and fabrication of water soluble mandrels

Mandrel is an important tool required in filament winding. The external shape of the mandrel should necessarily conform to the inside contour of the product being wound and should have adequate strength to withstand many steps involved in the fabrication, such as winding, curing and machining - operations. Hence, the selectiop of material for the mandrel and the design of the mandrel should be based, keeping the above manufacturing aspects in view, in order to produce reliable filament wound products which are dimensionally accurate and free from residual stresses

Liner for filament wound vessels

Utilisation of composite materials in the fabrication of13; high performance pressure vessels like solid propellant rocket motor cases presents a unique problem which is characteristic of composite materials. For the optimal design of motor cases, it is necessary to use high design stresses. As the motor cases are normally filament wound, embedding high strength fibres in a resin matrix whose strength and percentage elongation at failure are very much lower than that of the fibres, cracking of resin matrix take place under stress, at a stress value13; very much below the design stress. Hence, in order to utilise, the high specific strength of the fibres in filament wound pressure vessels, it becomes necessary to provide a 'barrier' or liner on the inner surface of the vessel to contain the pressurizing medium

Development of eproxy-glass-pre-impregnated rovings suitable for filament winding

The purpose of this programme was to develop pre-impregnated13; -epoxy rovings which are suitable for filament wound13; pressure vessels. Use of a preimpregnated winding material is necessary in the fabrication of aerospace structural components, for which predictable strength properties are important.properties such as resin content which adversely affect the of filament wound components, can be easily cona13; preimpregnated winding material is used in the Specially in winding large components, involving ble fabrication time, use ot wet winding technique resulting variation of the mechanical properties of the component is due to the low Viscosity resin systems normally employed wet winding. which are prone to set at ambient temperatures, resulting in variation of mechanical properties throughtout the wall thickness of the component

Development of epoxy-glass-pre-impregnated rovings suitable for filament winding

The purpose of this programme was to develop pre-impregnated13; glass-epoxy rovings which are suitable for filament wound13; pressure vessels. Use of a pre-impregnated winding material is necessary in the fabrication of Aerospace structural components, for which predictable strength properties are important. Material properties such as resin content which adversely affect the strength of filament wound components, can be easily 'Controlled when a pre-impregnated winding material is used in the fabrication. Specially in winding large components, involving considerable fabrication time, use of wet winding technique results in variation of the mechanical properties of the component. This is due to the low viscosity resin systems normally employed in wet winding, which are prone to set at ambient x2022;temperatures, resulting in variation' of mechanical properties through out the wall thickness of the component. 13; On the other hand, pre-impregnated materials can be produced13; in ready-to-use packages controlling the material properties13; accurately. Moreover, as prepregs contain partially polymerised resin, significant polymerisation of the resin does not take place during fabrication 'of the component.13; Following are some of the important advantages which can13; be realised with the use of pre-impregnated material in filament winding