The interaction between heparin and polylysine: a circular dichroism and molecular modelling study.

The sulfated polysaccharide heparin interacts with both poly-L- and poly-D-lysine, promoting the alpha-helix conformation in the polypeptide. Chemically modified heparins in which one of the three sulfate groups per disaccharide has been removed form the same type of complex with poly-L-lysine; when two of the three sulfate groups are removed this property is lost. Heparin oligosaccharides as small as the octasaccharide can still promote alpha-helix in poly-L-lysine; the hexa- and tetrasaccharides do not, but they do disturb to a lesser extent the dynamic conformation equilibrium associated with poly-L-lysine at pH7 (22 degrees C). A three-dimensional structure for the heparin/polylysine complex is proposed in which the helical heparin molecule and the alpha-helical polypeptide are side-by-side, not intertwining. The regular periodicity of sulfate group clusters along one side of the polysaccharide chain matches the periodicity of the polypeptide alpha-helix, allowing electrostatic interactions every three peptide turns between a heparin sulfate cluster and a zeta-amino group of the polylysine. The heparin octasaccharide is the smallest even-numbered oligosaccharide long enough for two such interactions to take place.

Acyclovir treatment of varicella in otherwise healthy children.

STUDY OBJECTIVE: To determine whether acyclovir administered orally affects the duration and severity of varicella in otherwise normal children. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: Patients' residence and university hospital clinic. PATIENTS: One hundred five children between 5 and 16 years of age with laboratory-confirmed varicella entered the study. Of the 102 who were included in the final analysis, 50 received acyclovir and 52 received placebo. INTERVENTION: Placebo or acyclovir was given orally four times daily, for 5 to 7 days. The acyclovir dose was adjusted as follows: 5 to 7 years of age, 20 mg/kg; 7 to 12 years, 15 mg/kg; and 12 to 16 years, 10 mg/kg. MEASUREMENTS AND MAIN RESULTS: Acyclovir recipients, compared with the placebo group, defervesced sooner (median, 1 day vs 2 days; p = 0.001), experienced onset of cutaneous healing sooner, as reflected by a decrease in number of lesions (median, 3 days vs 2 days; p = 0.002), and had fewer skin lesions (median, 500 vs 336; p = 0.02). Acyclovir did not significantly change the rate of complications of varicella (10% in the acyclovir group vs 13.5% among placebo subjects). Adverse drug effects were not observed. Acyclovir recipients had lower geometric mean serum antibody titers to varicella-zoster virus than their placebo counterparts 4 weeks after the onset of illness, but antibody titers in both groups were similar 1 year later. CONCLUSIONS: These results provide evidence that acyclovir is useful and well tolerated for treatment of varicella in otherwise healthy children.