The use of oral sucrose for procedural pain relief in infants up to six months of age: a randomized controlled trial.

The aim of this study was to evaluate the effectiveness of oral sucrose in decreasing pain during minor procedures in infants of 1-6 months corrected age. A blinded randomized controlled trial with infants aged 4-26 weeks who underwent venipuncture, heel lance or intravenous cannulation were stratified by corrected age into > 4-12 weeks and > 12-26 weeks. They received 2 mL of either 25% sucrose or sterile water orally 2 minutes before the painful procedure. Nonnutritional sucking and parental comfort, provided in adherence to hospital guidelines, were recorded. Pain behavior was recorded using a validated 10 point scale at baseline, during and following the procedure. Data collectors were blinded to the intervention. A total of 21 and 20 infants received sucrose and water, respectively, in the > 4-12-week age group, and 21 and 22, respectively, in the > 12-26-week age group. No statistical differences were found in pain scores between treatment and control groups at any data collection points in either age group. Infants aged > 4-12 weeks who did nonnutritional sucking showed statistically significantly lower median pain scores at 1, 2, and 3 minutes after the procedure than those who did not suck. Infants aged > 4-26 weeks exhibited pain behavior scores that indicated moderate to large pain during painful procedures; however, there was insufficient evidence to show that 2 mL 25% sucrose had a statistically significant effect in decreasing pain. Infants should be offered nonnutritional sucking in compliance with the Baby Friendly Health Initiative during painful procedures.

Synthesis, structure-activity relationships, and mechanism of drug resistance of D- and L-beta-3'-fluoro-2',3'-unsaturated-4'-thionucleosides as anti-HIV agents.

Various D- and L-2',3'-unsaturated 3'-fluoro-4'-thionucleosides (D- and L-3'F-4'Sd4Ns) were synthesized for the studies of structure-activity relationships. The synthesized D-2',3'-unsaturated 3'-fluoro-4'-thionucleosides did not show any significant antiviral activity against HIV-1, while unnatural L-nucleosides such as cytosine 34 (EC(50) = 0.13 microM; EC(90) = 1.7 microM) and 5-fluorocytosine 35 (EC(50) = 0.031 microM; EC(90) = 0.35 microM) derivatives exhibited potent anti-HIV activity without significant toxicity. Molecular modeling study shows that the 3'-fluorine atom of the d-2',3'-unsaturated cytidine triphosphate (D-3'F-4'Sd4CTP) experiences unfavorable electrostatic interaction with its own triphosphate moiety, resulting in the decreased binding affinity to wild-type HIV-1 reverse transcriptase (RT), which may be one of the reasons for the insensitivity of HIV-1 RT to these compounds. On the other hand, L-3'F-4'Sd4CTP binds to the active site of wild-type HIV-1 RT without steric hindrance and there is a possible hydrogen bonding between the 3'-fluorine atom and Asp185, which correlates with its potent anti-HIV activity. However, L-3'F-4'Sd4C 34 and L-3'F-4'Sd4FC 35 showed high cross-resistance to 3TC-resistant mutant (M184V) RT. Like other unnatural L-nucleosides, the unfavorable steric hindrance of the sugar moiety of L-3'F-4'Sd4CTP with the side chain of Val184 explains its significant cross-resistance to the M184V mutant.