PubMed Health⌕ Search

Biomedical subjects

J Tenovuo

Publications and source records attributed to J Tenovuo.

At least 37 records · Page 2Linked to original sources
PubMed1998

The effects of different (pseudo)halide substrates on peroxidase-mediated killing of Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans is a Gram-negative bacterium which has an important role in localized juvenile and in progressive periodontitis. It is sensitive to killing by the myeloperoxidase (MP)-hydrogen peroxide (H2O2)-chloride system which is part of the innate host defense mediated by polymorphonuclear leukocytes. Since it has been recently suggested that thiocyanate, instead of chloride, could serve as a main substrate for MP as for lactoperoxidase (LP) and salivary peroxidase, we investigated in this study the effect of both LP and MP systems on A. actinomycetemcomitans with different (pseudo)halide substrates, thiocyanate, chloride and iodide. The concentrations of the substrates were physiological for oral fluids, as was the concentration range of H2O2. Both peroxidases produced end products with identical antibacterial activity with thiocyanate and iodide. The oxidation of iodide resulted in the highest antimicrobial efficiency followed by chloride and thiocyanate. Addition of thiocyanate into either MP-H2O2-chloride or MP/LP-H2O2-iodide system abolished the bactericidal activity of the oxidized halide. However, the chloride did not affect the bactericidality of the MP-H2O2-iodide system, but when all 3 (pseudo)halide substrates were present no antimicrobial effect was recorded. Our study shows that the presence of thiocyanate in physiological amounts is able to prevent the bactericidal activity of halide-peroxidase systems in low H2O2 concentrations. These results explain why thiocyanate-peroxidase systems of either innate origin (saliva, crevicular fluid) or introduced by commercial oral hygiene products are most probably ineffective against A. actinomycetemcomitans in vivo. Further studies of halide/thiocyanate ratio are needed to develop products which are also effective against oral anaerobes.

Aggregatibacter actinomycetemcomitans↗
PubMed1998

Generation of bioluminescent Streptococcus mutans and its usage in rapid analysis of the efficacy of antimicrobial compounds.

The oral bacterium Streptococcus mutans was transformed by electroporation with a shuttle vector (pCSS945) containing insect luciferase gene from a click beetle (Pyrophorus plagiophthalamus) resulting in a bioluminescent phenotype. This S. mutans strain was used in experiments in which light emission was used as a rapid and, compared to conventional CFU counting, more convenient means of estimating the effects of various antimicrobial treatments. The basic parameters affecting in vivo light production by the strain were studied. It was found that pH 6.0 was optimal for incorporation of the substrate D-luciferin for the luciferase reaction. The optimum concentration of D-luciferin was approximately 150 microM at room temperature. Under optimum conditions the light emission in vivo increased rapidly to a constant level and thereafter had a decay of 0.6%/min when logarithmic-growth-phase cells were used. The light emission closely paralleled the numbers of CFU, giving a detectable signal from 30,000 cells and having a dynamic measurement range over 4 log CFU/relative light unit. The cells were treated with various antimicrobial agents, and the emitted bioluminescence was measured. With the bioluminescent measurements, the results were obtained within hours compared to the days required for agar plates, and also, the kinetics of the antibacterial actions could be followed. Thus, the light emission was found to be a reliable, sensitive, and real-time indicator of the bacteriostatic actions of the antimicrobial agents tested.

Adenosine Triphosphate↗
PubMed1998

Longitudinal analysis of the association of human salivary antimicrobial agents with caries increment and cariogenic micro-organisms: a two-year cohort study.

Previous studies of the possible associations of salivary antimicrobial agents with dental caries have given controversial results, obviously mainly because almost all studies have been cross-sectional. Our aim was to find out, in a two-year longitudinal follow-up study, the associations among selected salivary non-immune and immune antimicrobial variables, cariogenic bacteria, and caries increment. The study population was comprised of 63 subjects, all of whom had their 13th birthday during the first study year. In addition to a comprehensive dental examination at baseline and after 2 yrs, paraffin-stimulated whole saliva samples were collected in a standardized way at six-month intervals. Saliva samples were analyzed for flow rate, buffer effect, lysozyme, lactoferrin, total peroxidase activity, hypothiocyanite, thiocyanate, agglutination rate, and total and specific anti-S. mutans IgA and IgG, as well as for numbers of total and mutans streptococci, lactobacilli, and total anaerobic bacteria. Cluster analysis and Spearman-Rank correlation coefficients were used to explore possible associations between and among the studied variables. During the two-year period, a statistically significant increase was observed in flow rate, thiocyanate, agglutination rate, anti-S. mutans IgA antibodies, lactobacilli, and total anaerobes, whereas lysozyme, lactoferrin, and total and anti-S. mutans IgG antibodies declined significantly. Based on various analyses, it can be concluded that, at baseline, total IgG and hypothiocyanite had an inverse relationship with subsequent two-year caries increment, anti-S. mutans IgG antibodies increased with caries development, and mutans streptococci and lactobacilli correlated positively with both baseline caries and caries increment. Total anaerobic microflora was consistently more abundant among caries-free individuals. In spite of the above associations, we conclude that none of the single antimicrobial agents as such has sufficiently strong power to have diagnostic significance in vivo with respect to future caries.

Adolescent↗
PubMed1997

Generation of bovine immune colostrum against Streptococcus mutans and Streptococcus sobrinus and its effect on glucose uptake and extracellular polysaccharide formation by mutans streptococci.

Due to potential side-effects of active immunization by cariogenic mutans streptococci, oral administration of passively-derived antibodies could be a more acceptable way to reduce colonization and virulence of these microorganisms in human dentition. The aim of this study was to produce antistreptococcal immunoglobulins into bovine colostrum and explore the possible antibacterial mechanisms of these immunoglobulins against mutans streptococci. Specific serum IgG antibodies to whole cell antigens of both Streptococcus mutans and Streptococcus sobrinus increased rapidly in cows during immunization and were high also in the final whey-product. Low concentration (0.5% w/v) of bovine immune preparation inhibited significantly the incorporation of [14C]glucose by both S. mutans and S. sobrinus. Higher concentration (> 1%) was needed to inhibit the glucosyltransferase or fructosyltransferase activities of these bacteria. No such inhibitory effects were observed with the control preparation from the non-immunized cows. Our results indicate that bovine immune colostrum has a significant inhibitory potential against mutans streptococci, apparently dependent on the presence of specific IgG antibodies against S. mutans and S. sobrinus.

Animals↗
PubMed1997

Release of cariostatic agents from a new buffering fluoride- and xylitol-containing lozenge to human whole saliva in vivo.

A new buffering lozenge (sucking tablet) was developed for patients susceptible to dental caries and erosion, in particular for those with reduced salivary secretion. As active ingredients this lozenge comprises of a combination of xylitol, fluoride, calcium, phosphate, zinc and buffering compounds. To test the lozenge's activity in vivo, the release of ingredients was monitored in 19 healthy subjects for 22 min after sucking the lozenge was completed. In subjects with a normal salivary secretion rate the lozenge caused only a slight stimulation of saliva flow, but a significant elevation both in salivary pH and buffer effect was observed. Furthermore, fluoride, calcium and phosphate were effectively released into whole saliva with peak values 2-4 min after use. The same salivary parameters were also quantitated after 1 month's regular use (3 lozenges/day) but no consistent long-term changes were found. Salivary mutans streptococci and total anaerobic microflora did not change significantly during the long-term use. The results show that the buffering fluoride- and xylitol-containing lozenge, which also releases calcium and phosphate, is active in vivo but its serviceability as a remineralizing agent, in particular for elderly patients with reduced salivary flow rate, has to be analysed separately.

Administration, Oral↗
PubMed1997

Combined inhibitory effect of fluoride and hypothiocyanite on the viability and glucose metabolism of Streptococcus mutans, serotype c.

The separate and combined effects of peroxidase-generated hypothiocyanite (HOSCN/OSCN-) and F- ions on glucose uptake and growth of Streptococcus mutans ATCC 25175 were investigated. S. mutans cells were grown to late exponential or stationary growth phase, harvested, washed and suspended in 2.0 ml of sterilized human whole saliva supplemented with 10 mM D-glucose. This saliva-bacteria mixture was supplemented with 5-150 microM H2O2 at pH 5.0 or 6.5. At pH 5.0, up to 103 +/- 21 microM HOSCN/OSCN- was generated. After 20 h of incubation at 37 degrees C, the saliva-bacteria suspension exposed to HOSCN/OSCN- were plated on mitis salivarius agar plates and incubated anaerobically for 2 days. Identical experiments were made with F- ions (0.5, 1.0 and 5.0 mM). Both HOSCN/OSCN- and F- caused a significant dose-dependent growth inhibition at pH 5.0, whereas no inhibition was observed at pH 6.5. When F- and HOSCN/OSCN- were added simultaneously at pH 5.0, an additive effect of growth inhibition was observed. In glucose incorporation experiments the bacteria-saliva mixture was exposed to 1 microM HOSCN/OSCN-, 0.5 mM F- or both. F-, HOSCN/OSCN- or their combination in sterilized whole saliva at pH 5.0 caused 14.2, 67.8 and 74.2% inhibition, respectively. These observations indicate that F- and HOSCN/OSCN- ions have an additive inhibitory effect on S. mutans and therefore their combination is likely to be more antibacterial than either agent alone.

Cariostatic Agents↗
PubMed1997

Effects of open heart surgery on oral mucous host defence systems.

BACKGROUND: The immune response is affected by anaesthesia and surgery. This study was carried out on the effects of open heart surgery on the oral mucous host defence system, which is part of the common mucosal immune system. METHODS: Amylase, nonimmunological (lysozyme, myeloperoxidase, hypothiocyanite and thiocyanate) and immunological (IgA, IgG, and IgM) mucous host defence factors as well as oral bacterial flora were determined in the saliva of 18 patients undergoing open heart surgery preoperatively and on the 2nd, 3rd, and 7th postoperative days. To assess the specificity of the changes, the salivary flow rate and total protein content were also determined. RESULTS: Stimulated salivary flow decreased from 1.8 (1.3-2.2) ml/min (median; 25th and 75th quartiles) to 0.4 (0.3-0.5) ml/min by the 2nd postoperative day and to 0.4 (0.2-1.0) ml/min by the 3rd postoperative day (P < 0.001). Amylase, lysozyme, myeloperoxidase, total salivary peroxidase and thiocyanate levels increased, whereas hypothiocyanite levels decreased postoperatively (p < 0.01-0.001). Their total secretion rate, however, was reduced (P < 0.05-0.001) owing to the lowered salivary flow rate. IgG and IgM concentrations were raised on the 2nd, 3rd and 7th postoperative days (P < 0.05-0.001), and IgA concentrations on the 2nd postoperative day (P < 0.05). The total secretion of IgG and IgM as well as their salivary concentrations in relation to total protein concentrations also increased. The number of salivary anaerobically growing bacteria decreased postoperatively (P < 0.01), but the number of salivary streptococci remained unaffected. CONCLUSIONS: Open heart surgery decreases the salivary secretion of nonimmunological host defence factors and increases the salivary secretion of IgA, IgG and IgM.

Adult↗
PubMed1997

Salivary parameters of relevance for assessing caries activity in individuals and populations.

A review of the non-microbial salivary parameters with respect to their possible association with caries activity is presented. The parameters are limited to those which already are or at least in the near future will obviously be simple enough, also for clinical purposes. Salivary flow rate is undoubtedly the most important single parameter since the cariostatic activity or efficacy of practically all other salivary parameters depends on the flow rate. Flow rate as such has no linear association with dental caries but there seems to exist an individual "threshold" limit which is decisive for enhanced caries activity. This threshold limit varies among different individuals and therefore the so-called normal values for unstimulated or stimulated flow rate are more reliable on a population level than among individuals for screening purposes. In any individual a regular and longitudinal follow-up of the flow rate is of higher clinical value than only a single cross-sectional measurement. Salivary buffer effect has only a weak negative association with caries activity and again, this effect is of greater clinical significance on a population level. Since the decisive processes in caries attack occur within or under the dental plaque, the buffering effect of saliva is limited and obviously more important to screen for erosion-than caries-prone individuals. Although important for dental health, none of the salivary antimicrobial agents as such has shown any strong association with caries activity. The only ones with some evidence of a regulatory role are secretory IgA antibodies, hypothiocyanite ions, and agglutinins. However, the data are controversial and it seems that instead of measuring individual parameters, the assessment of saliva's functional properties (such as the ability to aggregate bacteria, prevent their adhesion to hydroxyapatite or sugar metabolism etc.) is more important for clinical purposes. Of the parameters involved in de- and remineralization process, only salivary fluoride content has some association with caries susceptibility but its diagnostic or predictive value is questionable.

Agglutinins↗
PubMed1996

Longitudinal analysis of human salivary immunoglobulins, nonimmune antimicrobial agents, and microflora after tonsillectomy.

In order to study the role of tonsils in the host defense in the oral region one pre- and two postoperative (1 and 6 months) whole saliva samples were collected from 25 young adults referred for tonsillectomy. Saliva samples were analyzed for selected host defense factors, representing both immune (total IgA, IgG, IgM, anti-Streptococcus mutans, anti-EBV, anti-CMV, and anti-adenovirus IgA and IgG) and nonimmunoglobulin (lysozyme, lactoferrin, salivary peroxidases, thiocyanate, hypothiocyanite, and agglutinins) mediators. Following tonsillectomy, a significant (P < 0.04) reduction was observed in specific IgG antibodies, suggesting that tonsils participate in local IgG response to oral antigens. Total IgM levels also decreased (P< 0.006), which may to some extent reflect reduced antigenic stimuli compared to preoperative status with frequent tonsillitis. Saliva-derived nonimmunoglobulin host defense factors, except lactoferrin, which declined significantly, remained normal throughout the study period. Our study indicates that tonsils play a role in local oral IgG-mediated immune response but tonsillectomy does not seem to lead to any significant long-term impairment of salivary defense capacity.

Adolescent↗
PubMed1996

Dental caries in relation to diet, saliva and cariogenic microorganisms in Tanzanians of selected age groups.

The relationship between diet and dental caries in a Tanzanian population was studied. Mutans streptococci, lactobacilli, yeasts, salivary flow rate as well as buffer effect were also analyzed. A random sample of 12-, 35-44- and 65- to 74- year olds was drawn from Msongola (rural) and Ukombozi (urban), Dar-es-Salaam. The mean of two 24-h recalls was used for the assessment of food intake. The percentage of those with at least one carious tooth ranged from 30% in the 12-year-olds to 80% in the oldest age group. The mean number of decayed teeth (DT) increased significantly with age (P = 0.000) but was not significantly associated with the area of residence. DT increased significantly (P = 0.048) with the number of snacks per day and was also associated with dietary sucrose (P = 0.025), total carbohydrates (P = 0.002) and fiber (P = 0.002). Among salivary variables lactobacilli (P = 0.000) correlated positively with DT. Our study did not reveal any strong association between total energy intake and dental caries in rural or urban populations in Tanzania but snacking and sucrose intake were significantly associated with caries, in particular in the urban area.

Adult↗
PubMed1996

Peroxidases, lactoferrin and lysozyme in peripheral blood neutrophils, gingival crevicular fluid and whole saliva of patients with localized juvenile periodontitis.

OBJECTIVE: The aim of this study was to examine the longitudinal association of selected non-immune anti-microbial host factors (peroxidases, lysozyme and lactoferrin) to the localized juvenile periodontitis (LJP) disease status. MATERIALS AND METHODS: Peroxidases, lysozyme and lactoferrin were quantitated from seven patients with LJP before and after periodontal therapy. Analyses were performed from simultaneously collected samples of peripheral blood polymorphonuclear leukocytes (PMNs), gingival crevicular fluid (GCF from diseased sites) and paraffin-stimulated whole saliva. Similar assays were done also from seven periodontally healthy controls. RESULTS: During untreated phase of LJP myeloperoxidase, lysozyme and lactoferrin concentrations were remarkably elevated in peripheral blood PMNs, also reflected in their high concentrations in GCF. All these values normalised with respect to healthy controls during the periodontal therapy. No similar longitudinal changes were seen in whole saliva but during therapy salivary peroxidase concentrations declined below the control values, in accordance with our previous observations in parotid saliva samples of LJP patients. CONCLUSIONS: In LJP the concentrations of lysozyme, lactoferrin and myeloperoxidase are significantly elevated in peripheral blood PMNs, also reflected in GCF. During periodontal therapy these values decline and approach those observed in healthy controls. No similar changes are seen in stimulated whole saliva.

Adolescent↗
PubMed1996

Effects of oral hygiene products containing lactoperoxidase, lysozyme, and lactoferrin on the composition of whole saliva and on subjective oral symptoms in patients with xerostomia.

This study evaluates the effects of two oral hygiene products containing nonimmunoglobulin antimicrobial agents on whole saliva and on subjective oral symptoms in patients with xerostomia. Twenty patients used a lactoperoxidase-system-containing toothpaste (Biotene) combined with the use of a mouthrinse (Biotene), comprising also lysozyme and lactoferrin, for 4 weeks. Saliva samples were collected at base line, after 4 weeks' use of the products, and at the end of a 4-week washout period. Samples were analyzed for selected biochemical and microbiologic factors. The effects on subjective oral symptoms were also recorded. A 4-week daily use of toothpaste and mouthrinse relieved the symptoms of oral dryness in 16 patients. The levels of salivary hypothiocyanite, lysozyme, lactoferrin, or myeloperoxidase activity did not change, but there was a significant decrease in salivary pH (P < 0.05), total peroxidase activity (P < 0.05), and total protein content (P = 0.01). In patients with the lowest salivary flow rates (n = 5) a significant (P > or = 0.04) increase was detected in salivary hypothiocyanite concentrations. No major changes occurred in salivary microflora. The products relieved subjective oral symptoms in most xerostomic patients, but this was not necessarily related to the presence of antimicrobial agents.

Adult↗
PubMed1995

Inhibition of herpes simplex virus type 1, respiratory syncytial virus and echovirus type 11 by peroxidase-generated hypothiocyanite.

The human mouth is an important route of viral transmission and evidence exists that human saliva can neutralize some viruses, e.g. herpes simplex type 1 (HSV-1) and human immunodeficiency virus (HIV) in vitro. However, little is known of the actual antiviral agents in saliva. We have analyzed how hypothiocyanite (HOSCN/-OSCN) ions, present in human saliva and generated by salivary peroxidase systems, affect the viability of three different types of viruses; HSV-1 (capable of inducing oral lesions), respiratory syncytial virus (RSV, respiratory infections), and echovirus 11 (EV 11, enteric diseases). Viral suspensions were pretreated (30 min) with HOSCN/-OSCN concentrations up to 180 microM both at pH 6.0 and 7.1 and inoculated into human gingival fibroblasts. The cultures were incubated at 37 degrees C for 18-48 h, fixed and the infected cells were counted after immunoperoxidase staining. HSV-1 was most sensitive to HOSCN/-OSCN with an IC50 of 8.5 microM at pH 6.0 and an IC50 of 20 microM at pH 7.1, respectively. RSV was inhibited by HOSCN/-OSCN only at pH 6.0 with an IC50 of 8.0 microM. EV 11 was also resistant at neutral pH, but sensitive at pH 6.0 with an IC50 of 68 microM. In contrast to HSV-1 and RSV, the inhibition of EV 11 was not dependent on the concentration of HOSCN/-OSCN. The inhibition was in all cases stronger at pH 6.0 than at neutral pH. Our results suggest that hypothiocyanite, a normal component of human whole saliva, in physiological concentrations effectively inhibits HSV-1 and RSV at acidic pH, whereas EV 11 is more resistant in vitro.

Adult↗
PubMed1995

Susceptibility of Streptococcus mutans and Streptococcus sobrinus to antimicrobial agents after short-term oral chlorhexidine treatments.

Effects of three different types of short-term applications (1-3 times during 1 week) of chlorhexidine (1 or 40%) on the susceptibility of 863 clinical isolates of Streptococcus mutans and 53 isolates of Streptococcus sobrinus from 58 subjects were studied. Chlorhexidine-resistant isolates were not found either before or after the treatment. The minimum inhibitory concentrations (MICs) to chlorhexidine of all isolates of S. mutans were < or = 1 microgram/ml, and of S. sobrinus < or = 2 micrograms/ml. S. mutans and S. sobrinus were also susceptible to ampicillin, penicillin, cefuroxime, and tetracycline. In conclusion, different short-term chlorhexidine regimens do not induce resistance in S. mutans or S. sobrinus and, furthermore, these species have so far retained their susceptibility to common antibiotics.

Ampicillin↗
PubMed1995

Effects of delmopinol on antimicrobial peroxidase systems and lysozyme in vitro and in human whole saliva.

Delmopinol is a new surface-active agent which can reduce plaque formation and gingivitis. This study was aimed to analyze whether delmopinol (0.0032-0.65 mM) interferes with the activity of two surface-active oral antimicrobial enzymes, salivary peroxidase and lysozyme. In addition to human whole saliva (pH 5.0 and 6.0), the experiments were done in 0.1 M phosphate buffer (pH 6.0) with purified lactoperoxidase (LPO) and myeloperoxidase (MPO). LPO and MPO were significantly inhibited in buffer by delmopinol concentrations > 6.5 mM and > or = 3.2 mM, respectively. No such inhibition was found for total peroxidase activity in mixed saliva. In vitro, delmopinol was found to desorb surface-bound peroxidases in an active form to the liquid phase. In further analyses, the possible effect of delmopinol on peroxidase-generated hypothiocyanite (HOSCN/OSCN-) was studied in saliva and buffer. No effect was found in buffer, but salivary HOSCN/OSCN- declined significantly with 6.5 mM delmopinol. This was obviously due to an enhanced decay of hypothiocyanite, rather than its reduced rate of formation. No delmopinol-related inhibition of lysozyme occurred in saliva or buffer. The results suggest that high concentration (6.4 mM -0.2%) of delmopinol may lower the concentrations of antimicrobial HOSCN/OSCN- in saliva but has no effect on human lysozyme.

Anti-Infective Agents↗
PubMed1995

Antimicrobial and mercury resistance in aerobic gram-negative bacilli in fecal flora among persons with and without dental amalgam fillings.

Antimicrobial resistance is more widespread than can be accounted for as being a consequence of the selection pressure caused by the use of antibiotics alone. In this study, we tested the hypothesis that a high mercury content in feces might select for mercury-resistant bacteria and thus for antimicrobial resistance linked to mercury resistance. Three subject groups with different exposures to dental amalgam fillings were compared. None of the subjects had taken antimicrobial agents during the three preceding months or longer. The group exposed to dental amalgam (n = 92) had 13 times more mercury in feces than the group that had never been exposed to amalgam (n = 43) and the group whose amalgam fillings had been removed (n = 56). No significant differences in either mercury resistance or antibiotic resistance in the fecal aerobic gram-negative flora of these subject groups were seen. The following antimicrobial resistance frequencies were detected with a replica plating method: > or = 1% resistance was seen in 40% of the subjects for ampicillin, 14% of the subjects for cefuroxime, 6% of the subjects for nalidixic acid, 14% of the subjects for trimethoprim, 19% of the subjects for sulfamethoxazole, and 25% of the subjects for tetracycline. The amount of mercury in feces derived from amalgam was not selective for any resistance factors in aerobic gram-negative bacteria, but antimicrobial resistance was widespread even among healthy subjects with no recent exposure to antibiotics.

Adolescent↗
PubMed1995

Comparison of the efficacy of 40% chlorhexidine varnish and 1% chlorhexidine-fluoride gel in decreasing the level of salivary mutans streptococci.

The aim of the study was to compare the efficacy of a 40% chlorhexidine (CHX) varnish (EC40, Certichem, Nijmegen, The Netherlands) with a 1% CHX-0.2% NaF gel in decreasing the level of salivary mutans streptococci (MS). The subjects were screened for a high level of MS using a Dentocult-SM strip method (Orion Diagnostica, Finland). In varnish groups with fluoride (VCHXF, n = 20) and without fluoride (VCHX, n = 19), the CHX varnish was applied on dry teeth using an ampoule and an anesthetic syringe with blunt needle, and removed after 15 min. In group VCHXF an additional 2.26% fluoride varnish (Duraphat, Woelm Pharma GmbH, Eschwege, Germany) was applied. The CHX-NaF gel treatment included the application of the gel with rubber cups and dental tape for 5 min on three occasions during a week in group GCHXF (n = 21). The level of MS (MSB agar) was significantly lower after 4 weeks than at baseline in VCHX (p < 0.001) and VCHXF (p < 0.05), but not after 12 weeks. In GCHXF a significant decrease (p = 0.001) was observed after 4 weeks only with the strip method. In VCHX and VCHXF the strip values for MS were still reduced after 12 weeks. In VCHX and GCHXF a small, although statistically significant, increase was observed in the total number of microorganisms after 4 and 12 weeks. Opinions on taste sensations associated with the treatments were generally negative, but least negative in the VCHXF group; fewer side effects were also reported in the VCHXF group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗