Oxidative degradation of biological substrates by hypochlorous acid has been examined under reaction conditions similar to those found in active phagosomes. Iron sulfur proteins are bleached extremely rapidly, followed in decreasing order by f3carotene, nucleotides, porphyrins, and heme proteins. Enzymes containing essential cysteine molecules are inactivated with an effectiveness that roughly parallels the nucleophilic reactivities of their sulfhydryl groups. Other compounds, including glucosamines, qumiones, riboflavin, and, except for N-chlorination, phospholipids, are unreactive. Rapid irreversible oxidation of cytochromes, adenine nucleotides, and carotene pigments occurs when bacterial cells are exposed to exogenous hypochlorous acid; with Escherichia coli, titrimetric oxidation of cytochrome was found to coincide with loss of aerobic respiration. The occurrence of these cellular reactions implicates hypochlorous acid as a primary microbicide in myelo.roxidase-containing leukocytes; the reactivity patterns observed are consistent with the view that bactericidal action results primarily from loss of energy-linked respiration due to destruction of cellular electron transport chains and the adenine nucleotide pool.Bacteria commonly lose their ability to divide within minutes of encountering phagocytosing leukocytes (1). Loss ofcell viability often occurs well before the onset ofcellular digestion as determined by physiological changes (2), macromolecular degradation (3, 4), or loss of macromolecular biosynthesis (5). The specific reactions giving rise to cellular death have not yet been identified, at least in part because leukocytes are capable ofinitiating a diverse set of processes which are potentially lethal (6, 7). Given the above observations, however, the microbicidal reactions must be among the first that attend interaction with the leukocyte.Reactions catalyzed by myeloperoxidase (MPOase) appear to make major contributions to the microbicidal-action of polymorphonuclear leukocytes (PMNs) (6, 7). The cell-free MPOase-H202-Cl-system is 'potentially microbicidal; chlorination of bacteria by the cell-free system (8, 9) and of macromolecular fractions during PMN digestion of bacteria (9) electrophile-nucleophile interactions involving association of electropositive chlorine with electron-rich centers on the substrate; reaction pathways are-correspondingly highly dependent upon medium-conditions, particularly H' and Cl-concentrations (14). With the exception ofamines and amino acids (11,12,15), the reactions of biological compounds with HOC1 are not understood (16).We report 'here the results of a survey of simple biological compounds which can be taken as prototypic ofvarious components of bacterial cells. :The data demonstrate that HOCI is strongly selective -toward nucleotides and compounds that are models for certain components ofrespiratory redox chains. This selectivity is shownito extend to bacterial cells. Table 1 were -determined from loss of their characteristic absorption bands when ...

BACKGROUND Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. RESULTS A total of 74 neonates were enrolled — 45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P = 0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P = 0.09). CONCLUSIONS Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.)

Substantial progress has been made in the characterization and development of mesoporous drug delivery systems for drug dissolution enhancement. However, more research is required to fully understand the drug release kinetic profile from mesoporous silica materials. Incomplete drug release from the carrier and the possibility of drug re-adsorption onto the silica surface need to be investigated. Issues to be addressed include the manufacturability and regulation status of formulation approaches employing mesoporous silica to enhance drug dissolution. While more research is needed to support the move of this technology from the bench to a commercial medicinal product, it is a realistic prospect for the near future.

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