Xylitol

https://www.ncbi.nlm.nih.gov/pubmed/15510034
Brown CL, Graham SM, Cable BB, Ozer EA, Taft PJ, Zabner J.
Source
Department of Otolaryngology--Head and Neck Surgery, University of Iowa College of Medicine, Iowa City, Iowa 52242-1093, USA.

OBJECTIVES:
Factors that alter airway surface liquid (ASL) ionic concentrations may influence the course of sinusitis. Xylitol has been shown to effect ASL ionic composition in vitro and to reduce nasal bacterial carriage, otitis media, and dental caries in vivo. We examined the effect of xylitol on experimental sinusitis in the rabbit model.

STUDY DESIGN:
Prospective randomized controlled study of xylitol, saline, and Pseudomonas aeruginosa administration to the rabbit maxillary sinus.

METHODS:
P. aeruginosa was administered to the sinuses of 26 New Zealand white rabbits. Saline was placed in the left maxillary sinus and xylitolin the right. The rabbits were randomly assigned to one of three groups: one, simultaneous administration of bacteria and solutions with bacterial analysis at 20 minutes, 11 rabbits; two, preadministration of solutions 1 hour before bacterial infection with analysis at 20 minutes, 11 rabbits; three, established sinusitis, 4 rabbits had daily injections of solutions for 5 days starting 7 days after P. aeruginosa administration.

RESULTS:
In group 1, 6.96% of injected bacteria were retrieved on the left (saline), whereas 0.095% were retrieved on the right (xylitol) (P = .034). In group 2, 5.64% of inoculum was recovered from the left and 2.89% from the right (P = .188). Group 3 demonstrated evidence of sinusitis with recovery of noninoculate bacteria. with no difference between right and left.

CONCLUSIONS:
Xylitol reduces experimental sinusitis when administered simultaneously with bacteria. Its effect in established sinusitis is less clear. A role may exist for xylitol in nasal irrigation fluid in human disease.

https://www.ncbi.nlm.nih.gov/pubmed/15377394
Durairaj L, Launspach J, Watt JL, Businga TR, Kline JN, Thorne PS, Zabner J.
Source
Department of Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. lakshmi-durairaj@uiowa.edu

BACKGROUND:
Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers.

METHODS:
This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline (10 ml) andxylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers.

RESULTS:
In naive mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49). There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38). There was no change in airway cellular response afterxylitol exposure in naive and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffynose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL cytokine levels were below the detection limits after xylitol exposure in normal volunteers.

CONCLUSIONS:
Inhalation of aerosolized iso-osmotic xylitol was well-tolerated by naive and atopic mice, and by healthy human volunteers.

https://www.ncbi.nlm.nih.gov/pubmed/11027360
Zabner J, Seiler MP, Launspach JL, Karp PH, Kearney WR, Look DC, Smith JJ, Welsh MJ.
Source
Howard Hughes Medical Institute, Departments of Internal Medicine, Pediatrics, and Physiology and Biophysics, and Nuclear Magnetic Resonance Facility, University of Iowa College of Medicine, Iowa City, IA 52242, USA. joseph-zabner@uiowa.edu

Abstract
The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.

https://www.ncbi.nlm.nih.gov/pubmed/10499281
Kontiokari T, Svanberg M, Mattila P, Leinonen M, Uhari M.
Source
Department of Paediatrics, University of Oulu, Finland. tero.kontiokari@oulu.fi

Abstract
Xylitol possesses anti-bacterial effects on pneumococci in vitro. To study the effect in vivo, the nostrils of 80 rats were inoculated with pneumococci. Intervention groups (n = 20) received either a xylitol diet or xylitol nasal sprays. The control groups were on a normal diet or had saline sprays. After 3 days, a quantitative bacterial culture and a PCR were done from the mucosal suspension. Neither the mean colony-forming unit counts nor the PCR counts differed statistically significant between the xylitol and control groups. Thus, we found that xylitol had no significant effect on pneumococcal mucosal colonisation.

https://www.ncbi.nlm.nih.gov/pubmed/22423849
Elamin K, Sjöström J, Jansson H, Swenson J.
Source
Department of Applied Physics, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.

Abstract
We present the first broadband dielectric spectroscopy (BDS) and differential scanning calorimetry study of supercooled xylitol-water mixtures in the whole concentration range and in wide frequency (10(-2)-10(6) Hz) and temperature (120-365 K) ranges. The calorimetric glass transition, T(g), decreases from 247 K for pure xylitol to about 181 K at a water concentration of approximately 37 wt. %. At water concentrations in the range 29-35 wt. % a plentiful calorimetric behaviour is observed. In addition to the glass transition, almost simultaneous crystallization and melting events occurring around 230-240 K. At higher water concentrations ice is formed during cooling and the glass transition temperature increases to a steady value of about 200 K for all higher water concentrations. This T(g) corresponds to an unfrozen xylitol-water solution containing 20 wt. % water. In addition to the true glass transition we also observed a glass transition-like feature at 220 K for all the ice containing samples. However, this feature is more likely due to ice dissolution [A. Inaba and O. Andersson, Thermochim. Acta, 461, 44 (2007)]. In the case of the BDS measurements the presence of water clearly has an effect on both the cooperative α-relaxation and the secondary β-relaxation. The α-relaxation shows a non-Arrhenius temperature dependence and becomes faster with increasing concentration of water. The fragility of the solutions, determined by the temperature dependence of the α-relaxation close to the dynamic glass transition, decreases with increasing water content up to about 26 wt. % water, where ice starts to form. This decrease in fragility with increasing water content is most likely caused by the increasing density of hydrogen bonds, forming a network-like structure in the deeply supercooled regime. The intensity of the secondary β-relaxation of xylitol decreases noticeably already at a water content of 2 wt. %, and at a water content above 5 wt. % it has been replaced by a considerably stronger water (w) relaxation at about the same frequency. However, the similarities in time scale and activation energy between the w-relaxation and the β-relaxation of xylitol at water contents below 13 wt. % suggest that the w-relaxation is governed, in some way, by the β-relaxation of xylitol, since clusters of water molecules are rare at these water concentrations. At higher water concentrations the intensity and relaxation rate of the w-relaxation increase rapidly with increasing water content (up to the concentration where ice starts to form), most likely due to a rapid increase of small water clusters where an increasing number of water molecules interacting with other water molecules.

https://www.ncbi.nlm.nih.gov/pubmed/22564094
Reed MD, McCombie BE, Sivillo AE, Thorne PS, Welsh MJ, March TH, McDonald JD, Seilkop SK, Zabner J, Durairaj L.
Source
Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA. mreed@LRRI.org

Abstract
Xylitol, a potential cystic fibrosis treatment, lowers the salt concentration of airway surface liquid and enhances innate immunity of human airways. The study objective was to evaluate the potential toxicity/recovery from a 14-consecutive day (7 days/week), facemask inhalation administration of nebulized xylitol solution in Beagle dogs. Aerosolized xylitol was generated through three Aerotech II nebulizers operating at approximately 40 psi driving pressure. Test article groups were exposed to the same concentration of aerosolized xylitol for 1, 0.5, or 0.25 h for the high, mid, and low exposures, respectively. A control group was exposed for 1 h to a nebulized normal saline solution. Animals were sacrificed the day following the last exposure or subsequently after 14 non-exposure days. Study endpoints included clinical observations, body weights, ophthalmology, and physical examinations, food consumption, clinical pathology, urinalyses, organ weights, and histopathology. Mean xylitol aerosol concentrations for all groups were approximately 3.5 mg/l. Mean total deposited doses to the pulmonary region were estimated as 21, 11, and 5 mg/kg, for the high-, mid-, and low-exposure groups, respectively. All dogs survived to the scheduled necropsy. No treatment-related findings were observed due to xylitol exposure in any end point examined. Lung findings (mild interstitial infiltration, macrophage hyperplasia, alveolitis, and bronchitis) were consistent among exposed and control groups. No exposure-related effect of xylitol in any parameter assessed was seen during or after the 14-day exposure in Beagle dogs. The No Observed Effect Level was the high-exposure level and suggests that inhaled xylitol is safe for clinical administration.

https://www.ncbi.nlm.nih.gov/pubmed/17768643
Nilsson H, Dragomir A, Ahlander A, Johannesson M, Roomans GM.
Source
Department of Medical Cell Biology, University of Uppsala, P.O. Box 571, 75123, Uppsala, Sweden. harriet.nilsson@mcb.uu.se

Abstract
Inhalation of hyperosmotic solutions (salt, mannitol) has been used in the treatment of patients with cystic fibrosis or asthma, but the mechanism behind the effect of hyperosmotic solutions is unclear. The relation between osmolarity and permeability changes was examined in an airway cell line by the addition of NaCl, NaBr, LiCl, mannitol, or xylitol (295-700 mOsm). Transepithelial resistance was measured as an indicator of the tightness of the cultures. Cell-cell contacts and morphology were investigated by immunofluorescence and by transmission electron microscopy, with lanthanum nitrate added to the luminal side of the epithelium to investigate tight junction permeability. The electrolyte solutions caused a significant decrease in transepithelial resistance from 450 mOsm upwards, when the hyperosmolar exposure was gradually increased from 295 to 700 mOsm; whereas the nonelectrolyte solutions caused a decrease in transepithelial resistance from 700 mOsm upwards. Old cultures reacted in a more rigid way compared to young cultures. Immuno-fluorescence pictures showed weaker staining for the proteins ZO-1, claudin-4, and plakoglobin in treated samples compared to the control. The ultrastructure revealed an increased number of open tight junctions as well as a disturbed morphology with increasing osmolarity, and electrolyte solutions opened a larger proportion of tight junctions than nonelectrolyte solutions. This study shows that hyperosmoticsolutions cause the opening of tight junctions, which may increase the permeability of the paracellular pathway and result in increased transepithelial water transport.