Changes in intraocular pressure following administration of suxamethonium and endotracheal intubation: Influence of dexmedetomidine premedication.

BACKGROUND: Use of suxamethonium is associated with an increase in intraocular pressure (IOP) and may be harmful for patients with penetrating eye injuries. The purpose of our study was to observe the efficacy of dexmedetomidine for prevention of rise in IOP associated with the administration of suxamethonium and endotracheal intubation. METHODS: Sixty-six American Society of Anaesthesiologists I or II patients undergoing general anaesthesia for non-ophthalmic surgery were included in this randomized, prospective, clinical study. Patients were allocated into three groups to receive 0.4 µg/kg dexmedetomidine (group D4), 0.6 µg/kg dexmedetomidine (group D6) or normal saline (group C) over a period of 10 min before induction. IOP, heart rate and mean arterial pressure were recorded before and after the premedication, after induction, after suxamethonium injection and after endotracheal intubation. RESULTS: Fall in IOP was observed following administration of dexmedetomidine. IOP increased in all three groups after suxamethonium injection and endotracheal intubation, but it never crossed the baseline value in group D4 as well as in group D6. Fall in mean arterial pressure was noticed after dexmedetomidine infusion, especially in the D6 group. CONCLUSION: Dexmedetomidine (0.6 µg/kg as well as 0.4 µg/kg body weight) effectively prevents rise of IOP associated with administration of suxamethonium and endotracheal intubation. However, dexmedetomidine 0.6 µg/kg may cause significant hypotension. Thus, dexmedetomidine 0.4 µg/kg may be preferred for prevention of rise in IOP.

Hydrogen bonding versus stacking stabilization by modified nucleobases incorporated in PNA.DNA duplexes.

The effects of incorporation of the modified nucleobases, 2,6-diaminopurine (D) (substituting for adenine) and 7-chloro-1,8-naphthyridin-2-(1H)-one (bicyclic thymine, bT) (substituting for thymine), that stabilize PNA.DNA duplex formation by increasing hydrogen bonding and/or base pair stacking interactions have been studied by thermal denaturation in terms of thermodynamics. Although the stabilizing effect of the bT base (in contrast to that of D base) is abolished upon addition of dimethyl formamide, thereby indicating that the stabilization is predominantly due to hydrophobic stacking forces, duplex stabilization was found to be enthalpic for both nucleobases. Increased stabilization (although not fully linearly) was observed with increasing numbers of modified bases, and single base sequence discrimination was only slightly compromised, but showed significant dependence on the sequence context.

On the stability of peptide nucleic acid duplexes in the presence of organic solvents.

Nucleic acid double helices are stabilized by hydrogen bonding and stacking forces (a combination of hydrophobic, dispersive and electrostatic forces) of the base pairs in the helix. One would predict the hydrogen bonding contributions to increase and the stacking contributions to decrease as the water activity in the medium decreases. Study of nucleobase paired duplexes in the absence of water and ultimately in pure aprotic, non-polar organic solvents is not possible with natural phosphodiester nucleic acids due to the ionic phosphate groups and the associated cations, but could be possible with non-ionic nucleic acid analogues or mimics such as peptide nucleic acids. We now report that peptide nucleic acid (PNA) (in contrast to DNA) duplexes show almost unaffected stability in up to 70% dimethylformamide (DMF) or dioxane, and extrapolation of the data to conditions of 100% organic solvents indicates only minor (or no) destabilization of the PNA duplexes. Our data indicate that stacking forces contribute little if at all to the duplex stability under these conditions. The differences in behaviour between the PNA and the DNA duplexes are attributed to the differences in hydration and counter ion release rather than to the differences in nucleobase interaction. These results support the possibility of having stable nucleobase paired double helices in organic solvents.

Unique properties of purine/pyrimidine asymmetric PNA.DNA duplexes: differential stabilization of PNA.DNA duplexes by purines in the PNA strand.

PNA.DNA duplexes are significantly stabilized by purine nucleobases in the PNA strand. To elucidate and understand the effect of switching the backbone in a nucleic acid duplex, we now report a thermodynamics study along with a solution conformations study of two purine/pyrimidine strand asymmetric duplexes and a strand symmetrical control by comparing the behavior of all four possible PNA/DNA combinations. In essence, we are comparing an identical basepair stack connected by either an aminoethyl glycine PNA or a deoxyribose DNA backbone. We show that the PNA.DNA duplexes containing purine-rich PNA strands are stabilized with regard to the thermal melting temperature and free energy as well as enthalpy (and concomitantly relatively less entropically disfavored). Based on our data, we find it unlikely that differences in counterion binding (identical ionic-strength dependence was observed), hydration (identical and insignificant water release was observed), or single-strand conformation can be responsible for the difference in duplex stability. The only consistent difference observed between the purine-rich PNA versus the pyrimidine-rich PNA in isosequential PNA.DNA duplexes is the significant increase in both binding enthalpy and entropy for the PNA.DNA duplexes containing pyrimidine-rich PNA in organic solvent, which would indicate that these duplexes are relatively enthalpically disfavored in water. Although our results so far do not allow us to identify the origin of the different stabilities of homopurine/homopyrimidine PNA.DNA duplexes, the evidence does point to a significant structural component, which involves enthalpic contributions both within the duplex structure and also from bound water molecules.

Influence of DNA structures on the conversion of sanguinarine alkanolamine form to iminium form.

Sanguinarine exhibits pH dependent structural equilibrium between iminium form (structure I) and alkanolamine form (structure II) with a pKa of 7.4 as revealed from spectrophotometric titration. The titration data show that the compound exists almost exclusively as structure I and structure II in the pH range 1 to 6 and 8.5 to 11, respectively. The interaction of structure I and structure II to several B-form natural and synthetic double and single stranded DNAs has been studied by spectrophotometric, spectrofluorimetric and circular dichroic measurements in buffers of pH 5.2 and pH 10.4 where the physicochemical properties of DNA remain in B-form structure. The results show that structure I bind strongly to all B-form DNA structures showing typical hypochromism and bathochromism of the alkaloid's absorption maximum, quenching of steady-state fluorescence intensity and perturbations in circular dichroic spectrum. The structure II does not bind to DNA, but in presence of large amount of DNA significant population of structure I is generated, which binds to DNA and forms a structure I-DNA intercalated complex. The nature and magnitude of the spectral pattern are very much dependent on the structure as well as base composition of each DNA. The generation of the structure I from structure II is significantly affected by increasing ionic strength of the medium. The conversion of structure II to structure I in presence of high concentration of DNA in solution is explained through formation of a binding equilibrium process between structure II and structure I-DNA intercalated complex.