Effects of guaifenesin on nasal mucociliary clearance and ciliary beat frequency in healthy volunteers.

STUDY OBJECTIVE: Mucociliary clearance is an important host defense function of the upper respiratory tract that requires the coordinated beating of cilia and results in the transport of mucus to the oropharynx. Guaifenesin is a commonly prescribed drug that is reported to improve the clearance of respiratory secretions. We hypothesized that guaifenesin increases nasal mucociliary clearance related to increases in ciliary beat frequency (CBF) and that a direct relationship exists between nasal CBF and nasal mucociliary clearance. DESIGN: Double-blind placebo-controlled crossover study. PARTICIPANTS: Ten healthy volunteers with a previous history of sinus disease. INTERVENTIONS: Subjects received guaifenesin or placebo on days 1 to 7 or days 14 to 21. MEASUREMENTS AND RESULTS: In vivo saccharine transit time (STT) was measured by noting the time in minutes required for the subject to taste a saccharin particle placed on the inferior turbinate of the naris. The CBF was determined by video microscopy on ten separate groups of beating ciliated nasal mucosal cells obtained by brushing immediately after each STT determination. We found that there was no significant change between the guaifenesin-or placebo-treated groups from baseline values of STT (p = 0.94) or CBF (p = 0.46). Regression analysis demonstrated no relationship between STT and CBF for repeated measures within subjects (mean r2 = 0.18; mean p = 0.66) and between STT and CBF when all paired measurements were combined across subjects (r2 = 0.47; p = 0.46). CONCLUSION: We conclude that guaifenesin exerts no measurable effect on in vivo nasal mucociliary clearance or ex vivo nasal ciliary motility in healthy volunteers with previous sinus disease. In addition, there appears to be no relationship between nasal STT measured in vivo and CBF measured ex vivo. The lack of correlation is most likely due to variations in CBF related to sampling artifacts introduced by the nasal brushing process.

Demonstration of the anti-viral activity of garlic extract against human cytomegalovirus in vitro.

The in vitro anti-viral activity of garlic extract (GE) on human cytomegalovirus (HCMV) was evaluated by tissue culture, plaque reduction and early antigen assay. A dose dependent inhibitory effect of GE was evident when GE was applied simultaneously with HCMV. But the effect was stronger when the monolayers were pretreated with GE. In addition, the anti-viral effect of GE persisted long in infected cells after its being removed from the culture medium. The strongest anti-viral effect of GE was demonstrated when it was applied continuously. It is therefore recommended that clinical use of GE against HCMV infection should be persistent and the prophylactic use of GE is preferable in immunocompromised patients.

Assessing research productivity: evaluating journal publication across academic departments.

Publications produced by faculty over a three-year period are used in analyzing the relative research productivity of basic and clinical science departments in a college of medicine. The citation ratings of the journals, the number of authors, and the byline position of the faculty member are used in various publication evaluation schemes. The departments vary almost tenfold in research productivity per faculty member. Results of the analysis demonstrate that the number of authors and the byline position influence departmental productivity rankings very little. Rankings are substantially affected, however, when the journals are weighted based heavily on citation ratings.

Stimulation of secretory antibody following oral administration of antigen.

IgA antibodies produced by plasma cells in secretory tissues associated with mucosal surfaces represent a major host defense against infectious agents. Precursors of these IgA-producing cells originate in gut-associated lymphoid tissue and, to a lesser extent, in bronchial-associated lymphoid tissue and migrate via the blood not only to gut but also to other mucosal tissues, forming a common mucosal immune system. Oral administration of antigen leads to priming of precursor cells in the gut and subsequent occurrence of specific secretory IgA (S-IgA) antibody in saliva, milk, tears, and the respiratory and genital tracts. On the basis of a review of the world literature, it has been concluded that oral live vaccines elicit higher antibody titers in remote-site secretions and in serum than do oral killed vaccines, which usually stimulate only relatively low levels of local secretory antibody. Oral immunization induces S-IgA in children and adults (including the elderly) without detectable adverse effects. Despite a number of remaining questions, oral immunization against extraintestinal infections is a promising area for future clinical studies.

Enhanced murine respiratory tract IgA antibody response to oral influenza vaccine when combined with a lipoidal amine (avridine).

The adjuvant activity of avridine, a synthetic lipoidal amine, incorporated in liposomes, was studied in mice immunized orally with killed influenza virus vaccine (A/PR/8/34, H1N1). Coadministration of avridine-containing liposomes and viral antigen enhanced the remote-site IgA antibody response in the respiratory tract without a concomitant serum antibody response or side effects. The results support the possible use of mucosal adjuvants for oral immunization against respiratory pathogens.

Age-dependent antibody response in mice and humans following oral influenza immunization.

In order to compare the antibody response in serum and secretions from healthy young subjects and the elderly (greater than 60 years), volunteers were immunized with the commercial inactivated influenza virus vaccine, by the usual (parenteral) route or orally. Also, young and old mice (mean age, 20 months) were orally immunized with live influenza virus. The older mice responded with a very slight rise in their serum and respiratory tract antibody levels compared with the young mice but showed no diminution in protection against lethal viral challenge. Elderly volunteers showed only slight serum antibody responses after parenteral immunization compared with the young. Neither group demonstrated a rise in serum antibody following oral immunization. With respect to the secretory IgA (SIgA) antibody response, certain differences were noted between the young and the elderly: the preimmunization levels of antibody to influenza virus were significantly greater in nasal secretions and saliva in the elderly as compared to the young volunteers, and the salivary antibody response was diminished in the elderly. This lack of a salivary antibody response in the elderly was explicable by the inverse relationship between the preimmunization SIgA antibody titers and the response to immunization. Oral immunization led to no more side effects than observed in the placebo control group.

Influenza specific antibodies in the female genital tract of mice after oral administration of live influenza vaccine.

In order to investigate the possible stimulation of antibodies in the genital tract by immunization female NMRI-mice were given orally a live influenza vaccine (A/PR/8/34, H1N1) on two occasions which were 10 days apart. Subsequently, virus specific IgA antibodies measured by an enzyme immunoassay in homogenates of urinary bladder, uterus and vagina and also in uterine washings. Specific IgA antibodies were not detectable in the sera of immunized mice. The high IgA titer in uterine washings, and in the homogenates suggests enhancement by vaccine of IgA antibody production in the genital tract.

Secretory antibody following oral influenza immunization.

Secretory IgA antibody may be important in protection against respiratory viral infections, and the concept of a common mucosal immune system offers the theoretical basis for the convenient stimulation of this antibody. Therefore, the oral route was compared with intramuscular injection in a double-blind, placebo-controlled study in young healthy volunteers. A killed influenza vaccine, given in enteric-coated capsules (total of 98 ug hemagglutinin of A/Bangkok) led to significant salivary and nasal IgA antibody rises in a 4-week period. The preimmunization titers in secretions were inversely correlated with the antibody rise after immunization. The orally administered vaccine was associated with no more side effects than placebo, in contradistinction to reactions following the intramuscular route. The latter route also was without significant effect in regard to a stimulation of secretory antibodies. The observed simultaneous induction of antibodies in saliva and nasal secretions following oral administration of killed vaccine gives further evidence of a common mucosal immune system and its possible clinical use.