The effect of continuous versus intermittent treatment with transdermal nitroglycerin on pacing-induced preconditioning in conscious rabbits

1. Tolerance to the hypotensive effect of nitroglycerin (NG) blocks preconditioning induced by rapid ventricular pacing (RVP) in rabbits. In the present work the effect of continuous versus intermittent treatment with transdermal nitroglycerin on the pacing-induced preconditioning phenomenon was studied in conscious rabbits. 2. RVP (500 beats min(−1) over 5 min) increased left ventricular end-diastolic pressure (LVEDP) from baseline 4.1±0.9 to postpacing 13.8±2.9 mmHg (P<0.001) with a right intraventricular ST-segment elevation of 1.25±0.13 mV, two indicators of myocardial ischaemia. These changes were significantly attenuated when the RVP period was preceded by a preconditioning pacing of the same rate and duration with an interpacing interval of 5 min. 3. Protection by preconditioning was abolished when the animals had been made tolerant to the vasodilator effect of 30 μg kg(−1) NG by the application of transdermal NG (approx. 0.07 mg kg(−1) h(−1)) over 7 days. Furthermore, transdermal NG per se attenuated both RVP-induced ST-segment elevation and LVEDP-increase over the 7 day period. 4. With intermittent transdermal NG treatment (12 h ‘patch on' vs ‘patch off'), neither development of vascular tolerance nor attenuation of the NG- or preconditioning-induced anti-ischaemic effects were observed. However, the severity of pacing-induced myocardial ischaemia was significantly increased during the ‘patch off' periods. 5. In a second set of experiments, postpacing changes in cardiac cyclic GMP and cyclic AMP levels were determined by means of radioimmunoassay in chronically instrumented anaesthetized open-chest rabbits with the same NG-treatment protocols. Preconditioning reduced postpacing increase in cyclic AMP with an increase in cyclic GMP concentrations in hearts of the untreated animals and in those given patches intermittently during both ‘patch on' and ‘patch off' periods. However, the preconditioning effect on either cyclic nucleotide was blocked in the tolerant animals. 6. Transdermal NG increased resting levels of both cardiac cyclic nucleotides in the non-tolerant but not in the tolerant state. The postpacing increase in cyclic AMP content was inhibited by transdermal NG, independent of vascular tolerance development, whereas, an increase in cyclic GMP content was exclusively seen in the non-tolerant animals. 7. We conclude that the anti-ischaemic effect of NG is independent of the cyclic GMP mechanism in the tolerant state. While intermittent NG therapy prevents development of vascular tolerance and preserves preconditioning, the nitrate-free periods yield an increased susceptibility of the heart to ischaemic challenges

Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen ' sd(left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions

Removal of Boron from Silicon by Solvent Refining Using Ferrosilicon Alloys

The distribution of boron between purified solid silicon and iron-silicon melt was evaluated to investigate the possibility of boron removal from silicon by solvent refining with iron-silicon alloys. The distribution coefficient, defined as the ratio of the mole fraction of boron in solid to that of liquid, was found to be strongly dependent on boron concentration. Solvent refining at lower temperatures resulted in smaller distribution coefficient values. The boron removal percentages for the lowest boron concentration examined in this study were, 70% (1583 K), 65% (1533 K), and 65% (1483 K). The values obtained for interaction parameter of boron on iron in solid silicon are as following: -813± 53 (1583 K), -830 ± 92 (1533 K), -863 ± 91 (1483 K). Lower temperature resulted in smaller distribution coefficient and higher silicon yield.This research is partly supported by Natural Sciences and Engineering Research Council of Canada (NSERC)