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Biomedical subjects

J Tenovuo

Publications and source records attributed to J Tenovuo.

At least 55 records · Page 3Linked to original sources

Salivary defense factors and oral health in patients with common variable immunodeficiency.

Studies of oral health in patients with common variable immunodeficiency have given controversial results. Obviously, one major factor modifying the oral health of these patients is saliva, in which the antibody-mediated defense is remarkably impaired compared to that of healthy subjects. However, the occurrence of nonimmunoglobulin (innate) antimicrobial agents in saliva of these patients is virtually unknown. Therefore, we analyzed both immune (total IgA, IgG, IgM, anti-Streptococcus mutans IgA, IgG, and IgM antibodies) and nonimmune (lysozyme, lactoferrin, salivary peroxidase, myeloperoxidase, hypothiocyanite, thiocyanate, and agglutinins) factors in whole saliva of 15 patients with common variable immunodeficiency. All patients were on Ig-replacement therapy (median duration, 10 years; range, 2-25 years), which had normalized their IgG but not their IgA or IgM levels both in serum and in saliva. Also, comprehensive clinical and microbiological analyses were made. The control group comprised 15 age- and sex-matched immunologically healthy subjects. The results showed no notable differences in dental caries, periodontal diseases, or salivary microorganisms but the patients had a history of more frequent oral mucosal lesions and respiratory infections. All innate, nonimmune salivary defense factors were equally abundant in the patients as in the controls, in many cases even at somewhat higher concentrations. These findings suggest that in spite of immunodeficiency, patients with common variable immunodeficiency display normal, perhaps even slightly elevated, levels of nonimmunoglobulin defense factors in whole saliva.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effect of antifungal agents on the in vitro susceptibility of Candida albicans to apo-lactoferrin.

The effect of subminimal inhibitory concentrations (MICs) of nystatin, amphotericin B, clotrimazole, miconazole and 5-fluorocytosine on the in vitro susceptibility of Candida albicans to physiological concentrations of apo-lactoferrin was investigated. Pre-exposure of C. albicans in 1:4 and 1:16 MICs of the antifungals resulted in an increased resistance to apo-lactoferrin-mediated cell death. Preincubation of Candida in tunicamycin (an agent that inhibits the synthesis of yeast cell-wall mannoproteins) and subsequent exposure to apo-lactoferrin enhanced the antifungal activity, whilst addition of ergosterol (a yeast cell-wall component) to the assay suspension had no significant effect. These results taken together indicate that apo-lactoferrin, an important component of saliva, interacts with cell-membrane constituents of C. albicans such as mannoproteins, and may modulate the effect of topical antifungal agents commonly prescribed for oral candidoses.

Amphotericin B↗

Antimicrobial factors, sialic acid, and protein concentration in whole saliva of the elderly.

Concentrations of salivary antimicrobial factors are well documented in children and young adults, but little information is available on such defense factors in healthy elderly persons. We determined the levels of total IgA, total IgG, lysozyme, lactoferrin, myeloperoxidase, salivary peroxidase, amylase, sialic acid, and total protein in a group of 71 subjects aged 76, 81, and 86 yr, as well as their correlations to paraffin-wax-stimulated salivary flow rate. Participants were either unmedicated (n = 67) or using medicines with no oral significance (n = 4). Statistically significant negative correlations existed between flow rate and total IgA, lysozyme, lactoferrin, sialic acid, and total protein. Concentrations of sialic acid and salivary peroxidase were highest in the oldest age group. Total IgA concentration was higher in women than in men, although men showed higher concentrations of sialic acid and higher sialic acid/total protein ratios. Subjects with poor gingival health had higher concentrations of total protein than did those with no need for periodontal treatment. Edentulous subjects with complete dentures showed significantly lower concentrations of IgG, lactoferrin, and myeloperoxidase than did dentate subjects. Our results suggest that, when compared with data from previous studies, concentrations of salivary antimicrobial agents do not decline with age in unmedicated elderly people. However, defense factors which are derived also from gingival crevicular fluid are decreased in the absence of teeth.

Aged↗

Lysozyme and lactoperoxidase inhibit the adherence of Streptococcus mutans NCTC 10449 (serotype c) to saliva-treated hydroxyapatite in vitro.

Lysozyme, lactoperoxidase and salivary peroxidase inhibit the metabolism and growth of mutans streptococci, but any possible effects on the adherence of these bacteria are unknown. In this study the effects of lysozyme and lactoperoxidase on the adhesion of 3H-labelled Streptococcus mutans (NCTC 10449, serotype c strain) to saliva-coated hydroxyapatite were studied at pH 5.0 and 7.0. Human whole saliva was either lysozyme-depleted and centrifuged, or sterilized and dialysed to achieve no detectable lysozyme and peroxidase activities; this modified saliva was used to form experimental pellicles. The incorporation of lysozyme (50-200 micrograms/ml) to the pellicle caused a significant (p < 0.01) reduction in the adherence of S. mutans without any loss of bacterial viability. Pretreatment of either saliva-coated apatite or S. mutans cells with lysozyme did not change the results but lysozyme bound more readily to bacteria than to the experimental pellicles. Also, lactoperoxidase (10-200 micrograms/ml) reduced significantly (p < 0.001) the adherence of S. mutans but, in contrast to lysozyme, in a dose-dependent way. The strongest inhibition of adhesion was found when both saliva-coated apatite and bacteria were pretreated with lactoperoxidase. This enzyme bound to experimental pellicles in preference to streptococci. A non-specific protein control, albumin, did not block the inhibition by lysozyme or lactoperoxidase. The inhibition of adherence of a serotype c strain of S. mutans to saliva-coated hydroxyapatite is a novel antibacterial mechanism for both lysozyme and lactoperoxidase.

Albumins↗

Fluoride inhibits the antimicrobial peroxidase systems in human whole saliva.

Fluoride (F-) ions at concentrations present in vivo at the plaque/enamel interface (0.05-10 mM) inhibited the activities of lactoperoxidase (LP), myeloperoxidase (MP) and total salivary peroxidase (TSP) in a pH- and dose-dependent way. The inhibition was observed only at pH < or = 6.5 and with F- concentrations > or = 0.1 mM. At pH 5.5 LP activity was inhibited by 85% and MP by 34% with 10 mM F-. TSP activity was also inhibited only at low pH (5.5) by approximately 25%. Furthermore, the generation of the actual antimicrobial agent in vivo, hypothiocyanite (HOSCN/OSCN-), of the oral peroxidase systems was inhibited by F-, again at low pH (5.0-5.5) both in buffer (by 45%) and in saliva (by 15%). This inhibition was observed only with the highest F- concentrations studied (5-10 mM). Fluoridated toothpaste (with 0.10 or 0.14% F) mixed with saliva did not inhibit TSP or HOSCN/OSCN- generation. This may have been due to the 'buffering' effect of toothpaste which did not allow salivary pH to drop below 5.9. We conclude that the F- ions in acidic fluoride products, e.g. in gels or varnishes (but not in toothpastes), may have the potential to locally inhibit the generation of a nonimmune host defense factor, HOSCN/OSCN/SCN-, produced by oral peroxidase systems. The possible clinical significance of this finding remains to be shown.

Animals↗

Flow rate and composition of whole saliva in rural and urban Tanzania with special reference to diet, age, and gender.

The association of flow rate and biochemical and microbiological characteristics of saliva with diet was studied in 83 12-year-old children and in 127 adults (84 in the age group 35-44 years, 43 in the age group 65-74 years) living in rural and urban communities in Tanzania. No significant differences were observed between the salivary flow rates of the rural and urban subjects. The mean salivary flow rates were slightly lower in women than in men and significantly lower in the 12-year-old children than in the two older age groups (p < 0.05). The buffer effect was higher in the rural than the urban population. Further, it was lower in women than in men (p < 0.001). Salivary protein, IgG, and sialic acid concentrations were significantly higher in the rural than in the urban population, whereas amylase activity and IgA concentrations were lower. Microbiological studies showed mutans streptococci in 97% of the rural and in 91% of the urban subjects (n.s.). Lactobacilli grew significantly less often in the rural than urban samples (p < 0.01). Analyses of 24-hour dietary recalls showed that the rural and urban diets differed. The proteins in the rural diet were largely of plant origin, while in the urban diet animal proteins dominated. The rural diet contained also less sucrose but more fibre (mainly from grain) than the urban diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of a lactoperoxidase-system-containing toothpaste on dental plaque and whole saliva in vivo.

The effects of a lactoperoxidase-system-containing toothpaste. Biotene, on saliva and dental plaque were studied. In a double-blind crossover study 20 healthy volunteers used an experimental (comprising the complete peroxidase system) or a placebo (without lactoperoxidase, KSCN, and glucose oxidase) toothpaste twice daily for 2 weeks separated by a 2-week washout period. At base lines and at the end of both test periods saliva and plaque samples were collected, and plaque pH changes were monitored. Saliva was analyzed for hypothiocyanite (HOSCN/OSCN-) and thiocyanate (SCN-) concentrations and salivary peroxidase activity. The amount of total streptococci, mutans streptococci, lactobacilli, and total anaerobic flora was determined both in saliva and in plaque samples. The accumulation and the acidogenicity of plaque were also quantitated. A 2-week daily use of Biotene had no effect on salivary flow rate, peroxidase activity, HOSCN/OSCN-, SCN-, or any of the monitored bacterial counts compared with the placebo toothpaste. The accumulation of dental plaque was not affected by the lactoperoxidase-system-containing toothpaste. The acidogenicity of plaque did not change significantly, nor did the two test dentifrices differ in their ability to inhibit the plaque pH drop caused by sucrose in subjects with normal salivary flow rate.

Adolescent↗

Agglutination of Streptococcus mutans serotype C cells but inhibition of Porphyromonas gingivalis autoaggregation by human lactoferrin.

The ability of various forms of human lactoferrin (LF) to agglutinate oral Streptococcus mutans, Strep. sobrinus, Strep. rattus, Strep. sanguis, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans cells was studied spectrophotometrically. Fe3+ saturated LF was unable to agglutinate these bacteria, whereas iron-free LF (apo LF) effectively agglutinated Strep. mutans cells but not the other bacteria. The efficiency and rate of agglutination of Strep. mutans were somewhat lower with apo LF than with human whole saliva. However, secretory IgA, phosphate and whole saliva almost totally abolished the apo LF-mediated agglutination of Strep. mutans, suggesting binding to the same target sites on bacterial cell surfaces, or to each other. The presence of exogenous iron (Fe2+, Fe3+), lactoperoxidase or serum albumin did not affect the agglutination by apo LF. Low Ca2+ (50-100 microns) slightly enhanced the agglutination by apo LF but higher concentrations (0.5-1.0 mM) totally blocked the apo LF-mediated agglutination of Strep. mutans. Both saliva and apo LF significantly delayed the rapid autoaggregation of P. gingivalis cells. Aggregation of P. gingivalis is considered a potential virulence factor and a protective mechanism against the host's cellular defences in the gingival crevice. These findings show a novel, strain-specific antibacterial mechanism for LF against Strep. mutans and P. gingivalis and adds a new compound to the group of agglutinating proteins in human saliva.

Agglutination↗

Immunohistochemical demonstration of androgen receptors in human salivary glands.

Androgen receptors were demonstrated in human salivary glands by immunohistochemistry using polyclonal antibodies. Fresh, clinically healthy salivary gland samples (two from minor, seven from parotid and eight from submandibular glands) of both sexes were used. Frozen tissue sections were incubated with the antibody against human androgen receptor and visualized by an indirect immunoperoxidase technique. Androgen receptors could be detected in all salivary tissues studied. Positive staining was confined to nuclei of almost all acinar cells as well as to the majority of nuclei in ductal cells. Very few of the nuclei of connective tissue and endothelial cells stained positively. The presence of androgen receptors in human salivary glands suggests possible direct effects of androgens on these tissues.

Adult↗

The fungicidal effect of human lactoferrin on Candida albicans and Candida krusei.

Five oral isolates each of Candida albicans and Candida krusei were studied for their sensitivity to the fungicidal effect of human lactoferrin. Significant inter- and intraspecies variations were observed and with most isolates the sensitivity of C. krusei to lactoferrin was greater than that of C. albicans. Fungicidal activity of lactoferrin was dose-dependent and observable only with the iron-free form of the molecule (apo-lactoferrin). Iron-saturated lactoferrin was ineffective against all isolates. Supernatant protein assays and scanning electron microscopy indicated cell surface alterations--leakage of proteins and formation of surface blebs--only in those Candida isolates that were sensitive to apo-lactoferrin. As lactoferrin is a common, non-immune, mucosal defence protein, its varying mode of action against C. albicans and C. krusei may be related to their different oral carriage rates.

Analysis of Variance↗

In vitro susceptibility of Streptococcus mutans to chlorhexidine and six other antimicrobial agents.

The susceptibility of Streptococcus mutans to chlorhexidine and to six commonly used, systemic antibacterial agents (amoxicillin, cefuroxime, penicillin, sulfamethoxazole-trimethoprim, tetracycline, and erythromycin) was studied for 424 clinical isolates from 116 children and students. The MIC of chlorhexidine for all isolates was < or = 1 micrograms/ml. No resistance to the other antimicrobial agents was detected. Although widely exposed to various antimicrobial agents, S. mutans has remained susceptible to common antimicrobial agents, most importantly to chlorhexidine.

Adult↗

Effects of a lactoperoxidase system-containing toothpaste on levels of hypothiocyanite and bacteria in saliva.

Lactoperoxidase (LPO)/H2O2/SCN(-)-system-generated hypothiocyanite ions (OSCN-) and hypothiocyanous acid (HOSCN) are inhibitory against a number of oral bacteria, including mutans streptococci. A commercially available toothpaste (Biotene) comprises the complete LPO system. Generation of HOSCN/OSCN- by Biotene was studied in vitro both in sterilized and nonsterilized saliva of 10 healthy subjects. The HOSCN/OSCN- yield ranged from 100 to 300 microM with Biotene, while the salivary levels of HOSCN/OSCN- before the addition of Biotene were 30.1 +/- 25.1 microM. Two in vivo trials were carried out. In the first study, resting saliva was collected from 12 individuals before, immediately after, and 2, 5, 10 and 20 min after brushing with Biotene to evaluate the in vivo generation and decomposition of HOSCN/OSCN-. In the second study, 26 healthy individuals attended a 1-month crossover trial with Biotene and a control toothpaste, Vademecum (no LPO system), both containing F- and xylitol. The salivary counts of total streptococci, mutans streptococci (MS), lactobacilli and the total flora (TF), as well as the peroxidase, thiocyanate ion and HOSCN/OSCN- levels were determined before and after 2 and 4 weeks daily use of the toothpastes. Twice-a-day use of Biotene for 1 month resulted in an elevation of 'resting levels' of HOSCN/OSCN-. No such effect was found with the control toothpaste. No significant changes were found in the salivary levels of total streptococci, MS, lactobacilli or TF after 1-month use of either toothpaste. The results show the capability of the LPO-system-containing toothpaste to elevate the salivary levels of HOSCN/OSCN-, although no bactericidal effect was observed.

Colony Count, Microbial↗

Intra- and inter-individual variation in salivary flow rate, buffer effect, lactobacilli, and mutans streptococci among 11- to 12-year-old schoolchildren.

Both intra- and inter-individual variation in salivary flow rate, buffer effect, and the levels of salivary mutans streptococci and lactobacilli were analyzed in 128 11-year-old children. The follow-up period was 9 months, with six saliva samplings done at regular intervals. Inter-individual variation was relatively large in paraffin-stimulated salivary flow rate: low (< 1.0 ml/min) and high (> or = 2.0 ml/min) flow rates were measured in 18% and 13% of the children, respectively. Intraindividual variation during the follow-up period was found in 63% of the boys and in 73% of the girls. The buffer effect stayed stable in all samplings in 59% of the boys and in 42% of the girls. Buffer effect was significantly (p < 0.001) lower in girls than in boys. Mutans streptococci were analyzed by a chair-side method (Strip mutans test) and by cultivation on mitis-salivarius-bacitracin (MSB) agar plates. The results of the two methods correlated highly significantly (r = 0.79, p < 0.001). With the Strip mutans test no variation in test scores occurred in 49% of all subjects in all six samplings, whereas the respective percentage for MSB scores was only 19%. No variation in salivary lactobacilli occurred in only 18% of the subjects, and in 13% the intraindividual variation was as high as > or = 3 logs. These results show that in young teenagers with a developing dentition, simultaneous changes in behavioral, hormonal, and dietary factors make single-point measurements of salivary factors too unreliable for caries-diagnostic or predictive purposes.

Agar↗

Fungicidal effect of human lactoferrin against Candida albicans.

Human lactoferrin (LF) in its iron-free state (apo LF), killed Candida albicans in a time- and dose-dependent way. The lethal effect was stronger at pH 7.0 than at pH 5.5 and maximum inhibition at neutral pH was achieved in 25 min when the fungal cells were exposed to LF in 0.05 mM KCl at 37 degrees C. Fe(3+)-saturated LF had no fungicidal activity. Apo LF-mediated killing was also temperature-dependent with enhanced inhibition at higher temperatures (37 degrees, 42 degrees C). The presence of 1 mM D-glucose did not affect the candidacidal activity of apo LF but both phosphate and bicarbonate ions at physiological salivary concentrations completely blocked the anti-fungal effect. Therefore it seems unlikely that LF belongs to the major host defence factors against oral candidosis.

Antifungal Agents↗

Salivary flow and composition in lymphoma patients before, during and after treatment with cytostatic drugs.

To investigate the effect of modern, intensive chemotherapy on salivary flow rate and composition, 79 patients suffering from Hodgkin's disease or non-Hodgkin lymphoma were studied before, during and after administration of cytostatic drugs. 49 patients (mean age 49.9 years, 30 men, 19 women) completed the 1-year study. All patients who received radiotherapy or medication other than cytostatics were excluded. The results showed no marked differences in stimulated salivary flow rates, buffering capacities and amylase and total protein concentrations between the beginning and the end of the 12 month trial. However, significant increases in albumin secretion into saliva and salivary lysozyme concentrations were observed. Total salivary IgG, IgA and IgM concentrations decreased significantly during the cancer therapy but values returned to the baseline levels after termination of treatment. Despite the well-known cytolytic effect of anticancer drugs, chemotherapy need not therefore be permanently detrimental to saliva.

Adult↗

Oral defense factors in the elderly.

Continuously increasing proportion of elderly people in the human population creates new challenges for the dental care. Because the microbial etiology of the most common oral diseases, dental caries, endodontal and periodontal diseases, is not substantially different in different age groups, the altered host response during aging may modify the progression of these diseases. Most prevalent and severe change in the oral defense is hyposalivation or xerostomia but aging as such does not seem to reduce neither parotid nor whole salivary flow rate. However, submandibular and minor salivary glands produce less saliva at old age which may be the reason for the frequently reported symptoms of oral dryness even if the stimulated flow rate is normal. Concomitantly to the changes in the flow rate the daily output of many saliva-mediated defense factors declines but age-related impairment has been described only for specific IgA response to external antigens, for salivary opsonic activity, and for T-lymphocyte function. The non-immunoglobulin defense factors seem to act with full capacity over the entire life-span. Therefore, elderly people with normal salivary flow rate possess no special risk group for the development of oral diseases.

Aged↗

Effects of chlorhexidine-fluoride gel treatments in mothers on the establishment of mutans streptococci in primary teeth and the development of dental caries in children.

In a longitudinal 3-year study, 151 children were followed for the colonization of the primary dentition by mutans streptococci (MS) and for the development of dental caries. At the age of 1 year, the child-mother pairs were divided into three groups on the basis of the levels of MS in maternal saliva. In the experimental group, the mothers had MS levels higher than 10(5) CFU/ml, and they were given chlorhexidine (1%)-sodium fluoride (0.2%) gel treatments twice a year for 3 years. Two control groups were formed. In control group 1, the mothers also had high levels of MS, but no gel was given. In control group 2, the mothers had low (< 10(5) CFU/ml) baseline levels of salivary MS, and no chlorhexidine-fluoride gel was used. In the total study population, 16, 42, and 54% of the children were colonized by MS by the age of 2, 3, and 4 years, respectively. Most children harbored only Streptococcus mutans, but 2 had both S. mutans and Streptococcus sobrinus, and 2 had only S. sobrinus. Twenty-eight percent of the MS-positive children developed caries by the age of 4 years, whereas 4 out of 27 children with dental caries did not have any detectable MS in their plaque samples. Both the colonization by MS and the caries incidence were highest in control group 1 and lower in the experimental group and in control group 2. These observations suggest that the reduction of maternal salivary MS at the time of tooth emergence may delay, or perhaps even prevent, the colonization of MS in the children's primary dentition with a concomitant decline in caries incidence, even in a population with an already low prevalence of dental caries.

Child, Preschool↗

Viability of Streptococcus mutans and Streptococcus sobrinus in whole saliva with varying concentrations of indigenous antimicrobial agents.

We have studied the possible relationship between indigenous salivary antimicrobial agents, indigenous mutans streptococci and the capability of added mutans streptococci to grow in saliva. Stimulated whole saliva was collected from 19 healthy donors. Saliva samples were sterilized, supplemented with glucose and inoculated with Streptococcus mutans or Streptococcus sobrinus. The mixtures were incubated for 20 h followed by counting of viable cells. Saliva samples were analysed, both before and after sterilization, for indigenous antimicrobial agents and the bacterial flora. The subjects could be divided into two groups: those (n = 9) whose saliva promoted and those (n = 10) whose saliva inhibited the growth of the inoculated streptococci. A statistically significant correlation (+0.82, p < 0.001) was found between the numbers of viable cells of S. mutans and S. sobrinus after incubation in saliva. The sterilization procedure reduced the content of all antimicrobial proteins. Salivary antimicrobial factors, or levels of indigenous mutans streptococci, did not differ between the two groups. We conclude that none of the individual salivary antimicrobial factors alone can explain the large individual differences in growth-promoting or growth-inhibiting patterns of saliva on S. mutans and S. sobrinus. Inter-individually, saliva either supports or inhibits the growth of mutans streptococci, indicating a similar response of these two species in relation to the properties of saliva.

Adult↗