Maternal tobacco use and extremely premature birth - a population-based cohort study.

OBJECTIVE: To study the associations of maternal tobacco use (smoking or use of snuff) and risk of extremely preterm birth, and if tobacco cessation before antenatal booking influences this risk. To study the association between tobacco use and spontaneous or medically indicated onset of delivery. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: All live singleton births, registered in the Swedish Medical Birth Register, 1999-2012. METHODS: Odds ratios (OR) with 95% confidence intervals (CI) were calculated using multiple logistic regression analysis. MAIN OUTCOME MEASURES: Extremely preterm birth (<28 weeks of gestation), very preterm birth (28-31 weeks), moderately preterm birth (32-36 weeks). RESULTS: Maternal snuff use (OR 1.58; 95% CI: 1.14-2.21) and smoking (OR 1.61; 95% CI: 1.39-1.87 and OR 1.91; 95% CI: 1.53-2.39 for moderate and heavy smoking, respectively) were associated with an increased risk of extremely preterm birth. When cessation of tobacco use was obtained there was no increased risk of preterm birth. Snuff use was associated with a twofold risk increase of medically indicated extremely preterm birth, whereas smoking was associated with increased risks of both medically indicated and spontaneous extremely preterm birth. CONCLUSIONS: Snuff use and smoking in pregnancy were associated with increased risks of extremely preterm birth. Women who stopped using tobacco before the antenatal booking had no increased risk. These findings indicate that nicotine, the common substance in cigarettes and snuff, is involved in the mechanisms behind preterm birth. The use of nicotine should be minimized in pregnancy. TWEETABLE ABSTRACT: Tobacco use increases risk of extremely preterm birth. Cessation is preventive. Avoid nicotine in pregnancy.

Dentin phosphoprotein sequence motifs and molecular modeling: conformational adaptations to mineral crystals.

Molecular modeling has been used to investigate structural features of oligopeptides derived from possible primary structure motifs in highly phosphorylated dentin phosphoprotein (PP-H), the predominant noncollagenous protein in dentin. It contains a large number of aspartate (Asp) and phosphoserine (Pse) residues, the latter proposedly crucial for the PP-H function as a mineral nucleator. In this work, computer fitting and subsequent structural adaptation of model peptides, built exclusively from Asp and Pse, to the known crystal structures of hydroxyapatite (HAP) and octacalcium phosphate (OCP) were performed. The results show that, when considering conformational energies of fitted single strand oligo-peptides, either crystal will serve. Within a narrow range, fitting to OCP was slightly favored, except for oligo(Pse-Pse-Asp-Asp), which showed a slightly better fit to HAP. Energy differences between crystal-adapted and non-adapted freely minimized peptides showed that oligo(Pse-Asp) docked to either HAP or OCP were the energetically most favored adaptations. Fitting of minimized triple anti-parallel beta-strands of oligo(Pse-Asp) or oligo(Pse-Pse-Asp), motifs found in published sequences of rat, mouse, and bovine PP-H, revealed that a (001) crystal face of HAP, but most likely not OCP, may be formed by these beta-sheet models. The former motif is more advantageous in this respect.

Effects of lesions of prefrontal cortex, amygdala, or fornix on behavioral sensitization to amphetamine: comparison with N-methyl-D-aspartate antagonists.

Behavioral sensitization to amphetamine involves the mesoaccumbens dopamine system and is accompanied by cellular changes in this system. Excitatory amino acid antagonists, when co-administered with amphetamine, prevent both behavioral sensitization and associated changes in the mesoaccumbens dopamine system. This suggests that excitatory amino acid-dependent events are critical to the initiation of sensitization. This study sought to identify excitatory amino acid projections required for sensitization, focusing on projections to the nucleus accumbens or ventral tegmental area. The major excitatory projections to the nucleus accumbens originate in the prefrontal cortex, amygdala and hippocampus. The prefrontal cortex and amygdala also send excitatory projections to the ventral tegmental area. Ibotenic acid lesions of the prefrontal cortex or amygdala and electrolytic lesions of the fornix were performed in rats. After one week of recovery, rats were treated with water or 2.5 mg/kg amphetamine for six days and challenged with amphetamine on day 8. Activity was tested in photobeam cages on days 1 and 8. On day 1, control and sham-lesioned rats exhibited stereotyped behaviors followed by a period of post-stereotypy locomotion. On day 8, sensitization was evident as an enhancement of both stereotypy and post-stereotypy locomotion. Co-administration of N-methyl-D-aspartate antagonists [MK-801 (dizocilpine maleate) or CGS 19755] with amphetamine prevented the development of sensitization of both stereotypy and post-stereotypy locomotion. Neither antagonist, however, prevented the expression of sensitization. None of the lesions completely mimicked these effects of N-methyl-D-aspartate antagonists. Lesions of hippocampal projections traveling in the fornix produced a general disinhibition of locomotor activity, but did not prevent sensitization of either stereotypy or post-stereotypy locomotion. Lesions of the prefrontal cortex failed to prevent sensitization of stereotypy was obtained following repeated amphetamine administration. However, like prefrontal cortical lesions, amygdala lesions prevented sensitization of post-stereotypy locomotion. When interpreted in the light of previous studies demonstrating the importance of the ventral tegmental area in the initiation of sensitization, the present results suggest a likely role for neuronal circuits involving the prefrontal cortex, amygdala and ventral tegmental area in the development of sensitization of post-stereotypy locomotion following repeated amphetamine administration. Such circuits may initiate sensitization through a mechanism involving excitatory amino acid regulation of the activity of mesoaccumbens dopamine neurons. Parallel circuits, involving other brain regions, may similarly contribute to sensitization of stereotyped behaviors.

MK-801 does not prevent acute stimulatory effects of amphetamine or cocaine on locomotor activity or extracellular dopamine levels in rat nucleus accumbens.

Recent work has shown that the development of behavioral sensitization to cocaine, amphetamine, and morphine is prevented by coadministration of N-methyl-D-aspartate (NMDA) antagonists such as MK-801. This suggests that NMDA receptors mediate long-term changes in neuronal responsiveness essential for the development of behavioral sensitization, similar to their role in other forms of neuronal plasticity. However, other studies, suggesting that NMDA receptor antagonists interfere with acute behavioral effects of psychomotor stimulants, call this interpretation into question and suggest that the ability of NMDA antagonists to prevent sensitization may reflect blockade of the acute effects of psychomotor stimulants. To examine this issue, behavioral and microdialysis studies assessed the effect of pretreatment with 0.1 mg/kg MK-801 on the ability of amphetamine and cocaine to stimulate locomotor activity and elevate extracellular dopamine (DA) levels in nucleus accumbens; this dose of MK-801 prevents sensitization when coadministered repeatedly with these stimulants. MK-801 pretreatment enhanced amphetamine-stimulated horizontal locomotion and stereotyped behavior. MK-801 pretreatment produced a modest attenuation of cocaine-stimulated horizontal locomotion, which may have reflected enhancement by MK-801 of certain components of cocaine-stimulated stereotypy. There was no effect of MK-801 pretreatment on the ability of amphetamine or cocaine to elevate extracellular DA levels in nucleus accumbens. These results suggest that the acute effects of cocaine and amphetamine on locomotor activity and extracellular DA levels are not prevented by MK-801, and that MK-801 must act through other mechanisms to prevent the development of behavioral sensitization.

Proton-metal distance determination in cobalt(II) stellacyanin by 1H nuclear magnetic resonance relaxation measurements including Curie-spin effects: a proposed structure of the metal-binding region.

1H nuclear magnetic resonance (1H NMR) experiments on Co(II)-substituted stellacyanin have been performed. Large paramagnetic hyperfine shifts are observed, the whole spectrum covering a range of 190 ppm. Experiments were mainly performed at 270 MHz from which temperature and pH* dependencies of the out-shifted resonances were reported, as well as determinations of the longitudinal (T1) and transverse (T2) relaxation times. These relaxation times are among other things, dependent on the individual proton-metal distance, and the aim of this work has been to determine these distances, by use of the Solomon-Bloembergen equations modified to include the so-called "Curie spin". The application of this method to a protein has not been reported earlier. Experiments were also performed at 100, 400, and 500 MHz in order to estimate the size of the Curie spin from the field dependence of the line widths. Furthermore, determination of the values for the rotational correlation time, tau r, and the effective magnetic moment, mu eff, was necessary for the present approach. With apostellacyanin, tau r was found to be (6.0 +/- 0.4) X 10-8 s. From the paramagnetic susceptibility of Co(II) stellacyanin, the value (4.53 +/- 0.03)beta was determined for mu eff. The proposed assignments of several paramagnetically out-shifted resonances. the proton-metal distances obtained, and the known peptide sequence of stellacyanin have allowed us to build a three-dimensional model of the metal site and its surrounding structure consistent with all the experimental data. It is revealed that both histidine ligands bind the metal with their 3-nitrogens. Also we find strong indications that a second sulfur atom is actually binding the metal, this being the long-sought-after fourth ligand. The model suggests that this sulfur belongs to Cys-59, which together with Cys-93 constitutes the disulfide bridge known to be present in the structure. A potential fifth ligand, an amide oxygen from Asn-47, is also found.

The metal site of stellacyanin: EXAFS studies of the Cu(II), Cu(I), Ni(II) and Co(II) derivatives.

Extended X-ray absorption fine structure (EXAFS) studies of Cu(II) (oxidized), Cu(I) (reduced), Ni(II) and Co(II) stellacyanin from Rhus vernicifera are reported. For Cu(II) stellacyanin, the coordination by three close ligands, viz. 2 N and 1 S, with the presence of smaller shells pointing to imidazole coordination, indicates similarities with the coordination in other so-called type 1 or 'blue'-copper proteins. Upon reduction, slightly longer ligand distances and an additional sulphur ligand are found. Ni(II) and Co(II) stellacyanin resemble Cu(I) and Cu(II) stellacyanin, respectively, in ligand distances, but have a tendency for three rather than two N (or O) ligands in the first shell. The results are compared with the three-dimensional model derived from 1H-NMR relaxation measurements for Co(II) stellacyanin, and are consistent with the proposal that apart from the three close ligands found in all blue-copper proteins, a sulphur from a disulphide bridge and the amide oxygen from an asparagine residue come to within coordinating distance of the metal in stellacyanin.

Direct measurement of the self-exchange rate of stellacyanin by a novel e.p.r. method.

A method for reconstituting the blue copper protein stellacyanin with the stable copper isotopes 63Cu and 65Cu is reported. Small differences in the e.p.r. spectra of the two isotopic forms of stellacyanin have been used to monitor the electron self-exchange reaction of stellacyanin by rapid-freeze e.p.r. methods. The self-exchange rate constant (k11) for stellacyanin has been determined as 1.2 X 10(5) M-1 X S-1 at 20 degrees C. This value is in close agreement with values obtained from less-direct methods.

The hospital experience of seat belt legislation in the county of Skaraborg, Sweden.

The effect of legislation for the compulsory wearing of seat belts by car drivers and front seat passengers was prospectively analysed in the county of Skaraborg, Sweden. After legislation fewer vehicle occupants were admitted to the hospitals, depsite a 40 per cent increase in crashes reported to insurance companies in the country. The frequency of seat belt wearing among injured victims was considerably lower than that recorded in regular traffic surveys. Significantly fewer head and neck injuries were suffered by restrained drivers than by unrestrained. Restrained front seat passengers had more thoracic injuries than unrestrained, but the degree of severity was less. The frequency of seat belt wearing by rear seat passengers was low, but they were injured as severely as front seat occupants. It seems important to insist on an increase in seat belt wearing for this category.