Minimum realisations and modelling of biological systems

A state variable model in the canonical form of Bucy is constructed from the given impulse response of a finite-dimensional, discrete-time, linear constant dynamical biological (arterial circulatory) system.     

Effect of verapamil on the non-adrenergic response of the field stimulated rat vas deferens

A comparison has been made, in the present study, between the effects of verapamil (reported to have smooth muscle depolarizing action) and K+ depolarization on the responses of noradrenaline, ATP and those of field stimulation on the vas deferens obtained from reserpinized rats. Field stimulation of the vas using single pulse (1 ms pulse width; supramaximal voltage) resulted in a fast twitch response reaching a maximum at 300 +/- 20 ms. Verapamil (6 X 10(-6) M) significantly potentiated this response. Verapamil potentiated the twitch component of the biphasic response resulting from field stimulation of the intrinsic nerves with repetitive pulses, while the tonic component was markedly inhibited. Verapamil enhanced the ATP (7 X 10(-5) M) response, while the phasic and tonic components of KCl (5.36 X 10(-2) M)-induced biphasic responses were nearly abolished. While the phasic component of the noradrenaline (7 X 10(-6) M) response remained unaltered in the presence of verapamil, the tonic component was markedly inhibited and rhythmicity following phasic component was markedly enhanced. Partial depolarization, achieved by increasing K+ concentration in the normal Krebs by two-fold i.e., to 11.8 mM, enhanced the responses of ATP, noradrenaline and the twitch resulted from the single pulse stimulation. The finding that verapamil potentiates the contractile response to exogenously applied ATP, which is believed to be the "noradrenergic" neurotransmitter in the vas deferens, suggests that this is the mechanism through which verapamil potentiates the twitch responses to field stimulation of the nerve supply.(ABSTRACT TRUNCATED AT 250 WORDS)     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Immobilisation stress induced analgesia in diabetic rats

Stress is known to produce analgesia. The pain threshold is altered in diabetes. We studied the effect of 1 hr of immobilisation stress on pain threshold in male Wistar rats. The same effect was tested in streptozotocin induced diabetic rats. The pain threshold of tail flick, vocalisation and vocalisation after discharge increased in the control group after the stress procedure. Significant analgesia was also obtained in diabetic rats, for flick and after discharge pain threshold. However the vocalisation threshold was not altered, probably due to the antagonistic action of glucose on opiate receptor at the level of brain stem.