Transgenerational effects of fetal and neonatal exposure to nicotine

A wide variety of in utero insults are associated with an increased incidence of metabolic disorders in the offspring and in subsequent generations. We have shown that fetal and neonatal exposure to nicotine results in endocrine and metabolic changes in the offspring that are consistent with those observed in type 2 diabetes. This study examines whether fetal and neonatal exposure to nicotine has transgenerational effects in the F2 offspring. Female Wistar rats were given either saline or nicotine (1 mg/kg/d) during pregnancy and lactation to create saline- and nicotine-exposed female F1 progeny. These F1 females were then bred to produce F2 offspring. We examined glucose homeostasis, serum lipids and fat pad weights, mitochondrial enzyme activity in skeletal muscle and blood pressure in these F2 offspring between 13 and 15 weeks of age. Offspring of nicotine- versus saline-exposed mothers had elevated fasting serum insulin concentrations and an enhanced total insulin response to the glucose challenge. This apparent insulin resistance was unrelated to changes in skeletal muscle mitochondrial volume or activity. The offspring of nicotine-exposed mothers also had elevated blood pressure. These data demonstrate that adverse effects of fetal and neonatal exposure to nicotine can influence aspects of metabolic risk in subsequent generations.     

Intellectual and language functions in children of mothers with epilepsy

PURPOSE: To compare the intellectual and language functions of children of mothers with epilepsy (CME) with that of controls matched for age and socioeconomic status. METHODS: Cases were CME, aged six years or more (n = 71), drawn from a prospective cohort in the Kerala Registry of Epilepsy and Pregnancy. Controls were 201 children of parents without epilepsy, matched for age and socioeconomic status. The outcome measures included Indian adaptation of Wechsler Intelligence Scale for children and MLT-a locally developed proficiency test for regional language. All relevant data were abstracted from the registry records. RESULTS: The Full Scale IQ and MLT scores were significantly lower for the cases (87.7 +/- 22.6 and 73.4 +/- 17.3) compared to controls (93.0 +/- 14.4 and 83.2 +/- 11.8). Compared to controls, CME scored poor on all subtests of MLT but their impairment was confined to only some of the subtests of IQ. Maternal education and maternal IQ significantly correlated with low IQ and MLT scores for CME whereas type of epilepsy, seizures during pregnancy or low birth weight did not have any significant association with these outcome measures. Polytherapy and higher dosage of antiepileptic drugs (AEDs) were associated with significant impairment in outcome measures. Infants with low developmental quotient at one year of age continued to have low scores on outcome measures at six years. CONCLUSIONS: Low maternal IQ, maternal education, and antenatal AED exposure were associated with significant impairment of intellectual and language functions for CME at six years.     

Coagulation markers in healthy human subjects exposed to diesel exhaust

BACKGROUND: Ambient particulate matter (PM) is associated with cardiovascular morbidity and mortality. It has been proposed that PM induces a pro-thrombotic process, increasing the risk of cardiovascular events, with some support from epidemiological and laboratory-based models. Diesel exhaust is a major contributor to urban PM, and we conducted a controlled human exposure of diesel exhaust in healthy subjects. OBJECTIVE: To evaluate diesel exhaust exposure effects on fibrinolytic burden (D-dimer), platelet number, and endothelial injury (von Willebrand's factor, VWF), inhibition of the fibrinolytic pathway (plasminogen activator inhibitor-1 [PAI-1]), and inflammation (C-reactive protein, CRP). MATERIALS AND METHODS: Randomized, crossover, double-blinded design, with 13 healthy participants exposed on three different days (>or=2 weeks washout) to diesel exhaust at 0 (filtered air), 100 microg PM(2.5)/m(3) and 200 microg PM(2.5)/m(3). We assessed diesel exhaust-associated changes in D-dimer, VWF, PAI-1 and platelets at 3, 6 and 22 h, and CRP at 22 h, after exposure initiation. RESULT: Significant changes did not occur in any primary endpoints. Among secondary endpoints, diesel exhaust (200 microg PM(2.5)/m(3)) effect on PAI-1 levels at 22 h was of borderline significance, with a 1.32-fold decrease after exposure to diesel exhaust (200 microg PM(2.5)/m(3)), relative to filtered air (CI 1.00 to 1.54). Diurnal patterns in D-dimer and PAI-1 were observed. CONCLUSIONS: In healthy individuals, exposure to 200 microg PM(2.5)/m(3) diesel exhaust did not affect primary pro-thrombotic endpoints. Thus, these data do not support a diesel exhaust-induced pro-thrombotic phenomenon. Replication of these studies should be carried out to ascertain whether or not they inform our mechanistic understanding of air pollution's cardiovascular effects.     

Single prolonged stress increases contextual freezing and the expression of glycine transporter 1 and vesicle-associated membrane protein 2 mRNA in the hippocampus of rats

Rats subjected to single prolonged stress (SPS) show enhanced HPA negative feedback, exaggerated acoustic startle response, and enhanced contextual freezing 7 days after SPS, and accordingly, SPS is an animal model of PTSD. To elucidate the influence of contextual fear on gene expression in the hippocampus of SPS rats, we used cDNA microarray followed by real-time quantitative PCR analyses to compare the hippocampal gene expression profiles between rats that were or were not subjected to SPS during exposure to contextual fear. In the behavioral experiments, spontaneous locomotor activity was measured 7 days after SPS. Twenty-four hours after footshock conditioning (7 days after SPS), freezing behavior was measured during re-exposure to the chamber in which footshock was delivered. Based on the behavioral analysis, rats subjected to SPS exhibited a significant enhancement of contextual freezing compared to rats not subjected to SPS, without any changes in locomotor activity. Analyses using cDNA microarray and RT-PCR showed that the hippocampal levels of glycine transporter 1 (Gly-T1) and vesicle-associated membrane protein 2 (VAMP2) mRNA in rats subjected to SPS were significantly increased relative to sham-treated rats. Administration of SPS alone did not affect the expression of these 2 genes. These findings suggest that the upregulation of Gly-T1 and VAMP2 in the hippocampus may be, at least in part, involved in the enhanced susceptibility to contextual fear in rats subjected to SPS.     

Vitamin D levels in people with multiple sclerosis and community controls in Tasmania,Australia

Abstract Background Adequate 25(OH)D levels are required to prevent adverse effects on bone health. Population-based data on factors associated with 25(OH)D levels of people with MS have been lacking. Objectives To examine the prevalence and determinants of vitamin D insufficiency in a population-based sample of MS cases and controls, and to compare 25(OH)D status between MS cases and controls, taking into account case disability. Methods We conducted a population based case-control study in Tasmania, Australia (latitude 41–43°S) on 136 prevalent cases with MS confirmed by magnetic resonance imaging and 272 community controls, matched on sex and year of birth. Measurements included serum 25(OH)D, sun exposure, skin type, dietary vitamin D intake and disability including EDSS. Results A high prevalence of vitamin D insufficiency was found in MS cases and controls. Among MS cases, increasing disability was strongly associated with lower levels of 25(OH)D and with reduced sun exposure. Cases with higher disability (EDSS > 3) were more likely to have vitamin D insufficiency than controls (OR = 3.07 (1.37, 6.90) for 25(OH)D ≤ 40 nmol/l), but cases with low disability were not (OR = 0.87 (0.41, 1.86)). Conclusion The strong associations between disability, sun exposure and vitamin D status indicate that reduced exposure to the sun, related to higher disability, may contribute to the high prevalence of vitamin D insufficiency found in this population-based MS case sample. Active detection of vitamin D insufficiency among people with MS and intervention to restore vitamin D status to adequate levels should be considered as part of the clinical management of MS.     

Systemic and developmental exposure to lead causes spatial memory deficits and a reduction in COX-2 immunoreactivity in the hippocampus of male rats

Chronic lead exposure during development is known to produce learning deficits. In the present study, we investigated the effects of developmental exposure to lead on spatial memory, as shown in the Morris water maze, and on expression of inducible cyclooxygenase-2 protein in the hippocampi of male rats. Rats were separated into four groups according to which concentration of lead acetate at which developmental stage they were exposed. One group was exposed maternally to lead acetate at a concentration of 250 parts per million (ppm), one group was exposed continuously to 250 ppm lead, one group was exposed maternally to 750 ppm lead, and one group was exposed continuously to 750 ppm lead. Increases were observed in both average escape latency and traveled distance of the rats in the maternally and continuously 750 ppm lead-exposed groups, indicating significant impairment of spatial memory. Quantitative immunostaining analysis by optical density measurement of brain sections from rats in all lead-exposed groups revealed a significant reduction (P < 0.001) in the intensity of cyclooxygenase-2 immunoreactivity in the Ammon's horn region 1 (CA1) and the dentate gyrus areas of the hippocampus. This reduction was concentration-dependent, with the maximum reduction observed in rats exposed to 750 ppm lead. Taken together, these findings suggest that exposure to lead causes spatial memory deficits in male rats and a significant reduction in cyclooxygenase-2 immunoreactivity in the CA1 and dentate gyrus areas.     

Effects of maternal smoking in pregnancy on prenatal brain development. The Generation R Study

Nicotine, as has been shown in animal studies, is a neuroteratogen, even in concentrations that do not cause growth retardation. In humans, there is only indirect evidence for negative influences of nicotine on brain development from studies on the association between maternal smoking in pregnancy and behavioural and cognitive development in the offspring. We investigated the associations of maternal smoking in pregnancy with foetal head growth characteristics in 7042 pregnant women. This study was embedded in the Generation R Study, a population-based prospective cohort study from foetal life until adulthood. Maternal smoking was assessed by questionnaires in early, mid- and late pregnancy. Head circumference, biparietal diameter, transcerebellar diameter and atrial width of lateral ventricles were repeatedly measured by ultrasound. When mothers continued to smoke during pregnancy, foetal head circumference showed a growth reduction of 0.13 mm [95% confidence interval (CI): -0.18, -0.09] per week compared to foetuses of mothers who never smoked during pregnancy. Biparietal diameter of foetuses with smoking mothers grew 0.04 mm (95% CI: -0.05, -0.02) less per week than that of foetuses of nonsmoking mothers. Atrial width of lateral ventricle was 0.12 mm (95% CI: -0.22, -0.02) smaller and transcerebellar diameter was 0.08 mm (95% CI: -0.15, -0.00) smaller if mothers smoked, but growth per week of these characteristics was not affected by maternal smoking in pregnancy. In conclusion, continuing to smoke during pregnancy leads to reduced growth of the foetal head. Further research should focus on the causal pathway from prenatal cigarette exposure via brain development to behavioural and cognitive functions.     

翼点入路鞍区手术上抬额叶对鞍区显露面积的影响

目的：探讨翼点入路不同上抬额叶高度对鞍区显露面积的影响。方法：5具成人头颅湿性标本模拟典型的翼点入路,分别测量额叶上抬0．5cm、1．0cm、1．5cm下鞍区手术间隙Ⅰ～Ⅳ的显露面积。结果：0．5cm、1．0cm、1．5cm各组间显露面积差异均有显著性（P〈O．005）。结论：对于鞍区手术,翼点入路上抬额叶可以显著影响鞍区手术显露。     

Coronary calcium scoring with MDCT: the radiation dose to the breast and the effectiveness of bismuth breast shield

OBJECTIVE: The purpose of our study was to determine the breast radiation dose during coronary calcium scoring with multidetector computerized tomography (MDCT). We also evaluated the degree of dose reduction by using a bismuth breast shield when performing coronary calcium scoring with MDCT. MATERIALS AND METHODS: The dose reduction achievable by shielding the adult (35 years or older) female breasts was studied in 25 women who underwent coronary calcium scoring with MDCT. All examinations were performed with a 16-MDCT scanner. To compare the shielded versus unshielded breast dose, the examinations were performed with (right breast) and without (left breast) breast shielding in all patients. With this technique the superficial breast doses were calculated. To determine the average glandular breast radiation dose, we imaged an anthropomorphic dosimetric phantom into which calibrated dosimeters were placed to measure the dose to the breast. The phantom was imaged using the same protocol. Radiation doses to the breasts with and without the breast shielding were measured and compared using the Student's t-test. RESULTS: The mean radiation doses with and without the breast shield were 5.71+/-1.1 mGy versus 9.08+/-1.5 mGy, respectively. The breast shield provided a 37.12% decrease in radiation dose to the breast with shielding. The difference between the dose received by the breasts with and without bismuth shielding was significant, with a p-value of less than 0.001. CONCLUSION: The high radiation during MDCT greatly exceeds the recommended doses and should not be underestimated. Bismuth in plane shielding for coronary calcium scoring with MDCT decreased the radiation dose to the breast. We recommend routine use of breast shields in female patients undergoing calcium scoring with MDCT.     

Measurements of occupational exposure to switched gradient and spatially-varying magnetic fields in areas adjacent to 1.5 T clinical MRI systems

PURPOSE: To determine if magnetic field exposure close to two clinical 1.5 T magnetic resonance imaging (MRI) scanners during image acquisition and when moving in the spatially-varying static magnetic field is compliant with European Union (EU) Directive 2004/40/EC (the Directive). MATERIALS AND METHODS: Using commercially available equipment we measured the magnetic flux density around the scanners during two clinical pulse sequences. The data was compared with frequency-dependent limits that will limit occupational exposure following transposition of the Directive into national law in 2008. The static magnetic field was measured around the scanners and the exposure from movement within this field was simulated. RESULTS: The whole-body exposure experienced when standing close to the face of the magnet exceeds the limits in the Directive on the two scanners tested during clinical sequences. Simulation of movement toward the scanner shows that speeds must be restricted to 1/5 of normal walking speed to comply with the Directive. CONCLUSION: EU Directive 2004/40/EC will have a major impact on the current use and future development of MRI due to limitations on exposure to time-varying gradient fields and movement within the spatially-varying static field. This will make interventional work impossible and routine MRI use impracticable in Europe.