Search PubMed⌕ Search

Biomedical subjects

A J Dunipace

Publications and source records attributed to A J Dunipace.

At least 19 recordsLinked to original sources
PubMed1996

Absence of detrimental effects of fluoride exposure in diabetic rats.

This study is part of a comprehensive programme to investigate fluoride toxicity and the hypothesis that fluoride ingested by "medically compromised' animals will result in altered physiological function. Its objectives were to monitor fluoride retention, tissue fluoride concentrations and genetic variables in diabetic and control rats chronically exposed to fluoride, and to determine whether or not adverse effects occurred. Male, Zucker fatty diabetic rats and Zucker age-matched lean controls were fed a low-fluoride diet ( < 1.2 parts/10(6) F-) ad libitum and received 0, 5, 15 or 50 parts/10(6) fluoride in their drinking water for 3 or 6 months. Fluoride metabolic balance was determined for 4 days before the end of each study phase. Plasma and urine were analysed for biochemical markers of tissue function, and plasma, urine, faeces and tissues were analysed for fluoride. Bone marrow cells from animals killed after 6 months of treatment were examined for frequency of sister chromatid exchange, a marker of genetic damage. The diabetic rats consumed, excreted and retained significantly greater amounts of fluoride than the controls (p < 0.05). There were dose-related increases in fluoride excretion, retention and tissue concentrations in both classes of animals, which were significantly greater in the diabetic rats. In spite of greater amounts of fluoride in the tissues of diabetic animals, there was no evidence, under these experimental conditions, that any of the fluoride exposures tested caused measurable adverse effects on the physiological, biochemical or genetic variables that were monitored.

Analysis of Variance↗
PubMed1996

An in vitro microbial model for studying secondary caries formation.

Secondary caries is a major reason for the replacement of restorations. Because it is hypothesized that the development of secondary caries is closely associated with pathogenic oral bacteria, an in vitro microbial model has been developed to produce secondary carious lesions. A mixture of overnight cultures of Streptococcus mutans and Lactobacillus casei in dextrose-free trypticase soy broth, supplemented with 5% sucrose (TSBS), at 37 degrees C was used in this model as the inoculum for the experimental groups. Uninoculated control groups were incubated with medium only. Groups of human tooth specimens restored using composite, together with their respective controls, were exposed for 7 or 12 days to circulating cycles of TSBS (30 min each, 3 times per day) and a mineral wash solution (for a total of 22.5 h per day), at 37 degrees C. The pH of the experimental groups dropped to 4.l-4.5 during the test periods. The pH of the control groups remained at 6.8-7.0. The inoculated bacteria remained viable throughout the study. No contamination of experimental or control samples occurred. Laser scanning confocal microscopy demonstrated the development of incipient surface and wall lesions in all the specimens of experimental groups in as few as 7 days. Reproducibility of the model was confirmed in a second investigation. Therefore, it was concluded that this model can be used for studying the microbial etiology and prevention of secondary caries.

Composite Resins↗
PubMed1996

Measurement of enamel demineralization using microradiography and confocal microscopy. A correlation study.

Substantial amounts of tooth minerals are lost during dental caries formation. Transversal microradiography, a well-accepted method used to quantify mineral loss, is a time-consuming technique which requires a thin enamel section (100 microns) and involves the use of x-rays. In an attempt to solve these difficulties, a procedure has been developed in which a human tooth specimen with demineralized enamel is cut in half (HT), stained with a fluorescent dye (rhodamine B) and analyzed using a laser scanning confocal microscope. A series of three studies was conducted to correlate measurements of enamel demineralization obtained from enamel thin (100 microns) sections (TS) using transversal microradiography with three parameters (area of the lesion; total and average dye fluorescence intensities) measured on the same TS or on a thicker section (HT) of the same specimen by laser scanning confocal microscopy. Results showed that a 0.1 mM rhodamine B solution provided the most adequate imaging conditions for confocal microscopy. Pearson's correlation coefficients, calculated between microradiography and confocal microscopy data obtained using a 0.1 mM rhodamine B solution, were: delta Z vs. HT lesion area = 0.95; delta Z vs. HT total fluorescence = 0.80; delta Z vs. HT average fluorescence = 0.74; delta Z vs. TS lesion area = 0.95; delta Z vs. TS total fluorescence = 0.74; delta Z vs. TS average fluorescence = 0.55. All these correlations coefficients were statistically significant (p < 0.01). It is concluded that in enamel demineralization studies statistically significant correlations exist between parameters measured using transversal microradiography and parameters quantified using confocal microscopy.

Analysis of Variance↗
PubMed1995

Effect of aging on animal response to chronic fluoride exposure.

This study was conducted to test the hypothesis that physiological changes which occur during aging increase the biological impact of fluoride and reduce the threshold of safe fluoride exposure. Four groups of rats were fed a low-fluoride diet (< 1.2 ppm) ad libitum and received 0, 5, 15, or 50 ppm fluoride in their drinking water. Animals were killed after three, six, 12, or 18 months of treatment. Blood and urine were monitored for biochemical markers of tissue function, and plasma, urine, feces, and representative tissues were analyzed for fluoride. In addition, bone marrow cells from animals killed after 18 months of treatment were examined for frequency of sister chromatid exchange (SCE), a marker of genetic damage. Study results indicated that, within treatment groups, fluoride intake, excretion, and retention did not change significantly between three and 18 months. Fluoride concentration in soft tissues did not change with treatment duration in the fluoride-treated animals. Mineralized tissue fluoride concentration and the total fluoride in the carcasses increased continually as the animals aged. In spite of significant, dose-related differences in tissue fluoride levels which occurred in all age groups in this study, there were no indications that increased fluoride in the tissues caused any adverse physiological or genotoxic effects. None of the monitored clinical "wellness" markers of tissue integrity and function was altered by fluoride in a clinically significant manner. Therefore, there was no evidence from this study that aging reduces the threshold of safe chronic fluoride exposure.

Age Factors↗
PubMed1995

Fluoride reduces bone strength in older rats.

In response to recent concerns about the effect of water fluoridation on hip fracture rates, we studied the influence of fluoride intake on bone strength. Four groups of rats were fed a low-fluoride diet ad libitum and received 0, 5, 15, or 50 ppm of fluoride in their drinking water. Animals were euthanized after 3, 6, 12, or 18 months of treatment. Mechanical strength of the right femur was measured by three-point bending. Fluoride content for the left femur was measured, and static histomorphometric measurements were made on a lumbar vertebra. Femoral failure load was not significantly decreased in rats treated for 3 and 6 months, but was decreased as much as 23% in rats treated 12 and 18 months at 50 ppm fluoride. Extrapolation from regression equations predicted that older rats lose 36% of femoral bone strength when bone fluoride content is increased from 0 to 10,000 ppm, while younger rats will lose only 15%. Thus, the decreased strength appeared to be due to the combined effects of fluoride intake and age on bone tissue and was not associated with a decrease in bone density or mineralization defects. There were only small effects of fluoride on bone histomorphometry. Fluoride intake at high levels had no negative effects on bone mineralization. Fluoride intake was associated with slight increases in trabecular bone volume and trabecular thickness, but these effects could not be demonstrated consistently. The mechanism by which large amounts of fluoride affect bone strength more severely in older animals is unknown.

Aging↗
PubMed1994

Degradation of insoluble bovine collagen and human dentine collagen pretreated in vitro with lactic acid, pH 4.0 and 5.5.

The purpose of the study was to test the hypothesis that both insoluble pure type I collagen from bovine Achilles tendon and dentine collagen in root dentine powder from human teeth required acid pretreatment for subsequent degradation by trypsin, a non-specific protease. Pure type I collagen or dentine powder was treated with lactic acid, at pH 4 or 5.5, or distilled, deionized water (pH 7) as a negative control. After incubation at 37 degrees C for 24 h, extracts of pure type I collagen solutions were analysed for soluble collagen with the hydroxyproline assay. Extracts of dentine powder solution were analysed for Ca2+, total protein, final pH, and hydroxyproline. Residual, undegraded pellets were washed and then treated with trypsin or collagenase. After 24 h of incubation, the soluble fractions from the enzyme-treated pure type I collagen and dentine powder solutions were analysed for hydroxyproline. Results showed that almost no pure type I collagen was degraded during acid pretreatment. Trypsin degraded significantly more pure type I collagen in the pH 4-treated group than in the other groups. Collagenase degraded about 70% of the pure type I collagen irrespective of acid pretreatment. While acid pretreatment at pH 4 did not degrade dentine collagen, data from Ca2+ analyses and collagen breakdown by trypsin suggested that pretreatment at pH 4 demineralized and denatured dentine collagen so that the collagen could be subsequently degraded by enzymes. After pretreatment at pH 4, about 27 and 57% of the dentine collagen was degraded by trypsin and collagenase, respectively, in contrast to minimal degradation of non-acid-treated dentine collagen by the same enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Achilles Tendon↗
PubMed1994

An in vitro model for studying the efficacy of fluoride dentifrices in preventing root caries.

This investigation tested and validated an in vitro model for studying the effects of fluoride on human dentin mineral content and fluoride uptake. Four studies examined the effects of different concentrations of fluoride, established dose-response profiles with NaF and Na2PO3F, and tested commercial dentifrices. A 7- or 14-day cyclic treatment regimen involved four 1-min exposures of sound human dentin specimens to the treatment agents, a 4-hour acid challenge period, and 20 h in human saliva daily. Mineral content was analyzed by image analysis microradiography and fluoride assays were performed using a microdrill biopsy technique. Data from these studies established the ability of the in vitro model to provide reproducible results, to demonstrate significant dose-related differences in the effects of both NaF- and Na2PO3F-containing treatments on dentin fluoride uptake and demineralization, and to detect a fluoride-induced reduction in dentin caries, relative to a nonfluoride control, similar to results established in a clinical trial.

Biopsy↗
PubMed1992

Mutagenic potential of toluidine blue evaluated in the Ames test.

Toluidine blue is a vital, metachromatic thiazine dye which is used as an adjunct in clinical examination for the early detection of asymptomatic recurrent or secondary primary carcinoma in individuals who are at high risk for developing oral cancer. Because available data on the mutagenicity of toluidine blue was limited and contradictory, this study was conducted to evaluate the mutagenic potential of toluidine blue in the in vitro Ames Salmonella test. Tester strains TA97a, TA98, TA100 and TA102 were used. Toluidine blue was tested at concentrations of 0.1, 1.0, 10, 50, 100, 250 and 500 micrograms/plate, with and without S9 microsomal activation, and positive and negative controls were included. Results from tests without S9 showed a significant increase (p less than 0.05) in number of revertants in TA102 and in TA97a with 50 and 100 micrograms toluidine blue/plate, respectively. In tests with S9 activation, doses of toluidine blue ranging from 10 to 250 micrograms/plate induced dose-related increases in the number of revertants in all 4 strains. The results of this study indicate that toluidine blue has a mutagenic effect in the Ames test.

Analysis of Variance↗
PubMed1992

Sample size considerations in designing studies with intra-oral models.

Especially during recent years, the use of pre-clinical models for predicting the efficacy of fluoride systems has assumed greater importance within the scientific community. Originally utilized primarily to screen experimental fluoride delivery systems, preclinical models are now being considered as predictors of clinical efficacy in lieu of controlled clinical caries trials. Of the various preclinical models presently available, human intra-oral models have the greatest potential for reflecting intended usage conditions and therefore may be the most meaningful models for predicting clinical efficacy. However, only with the proper consideration of numerous critical variables can studies using intra-oral models be appropriately designed to achieve the desired objectives. Clearly, these models must provide relevant information in a manner which reflects clinically established cariostatic activity and be capable of detecting established differences in the amount of cariostatic activity, i.e., dose-response effects. Three sources of variation must be considered before an appropriate study design and sample size can be chosen. Based on fluoride uptake data from an intra-oral model with proximally-located enamel specimens, estimates of variation among subjects, within subjects, and among specimens within subjects were obtained. Multiple specimens per panelist do not affect the first two sources of variation. Thus, the number of panelists, and not the number of specimens, is of primary importance when pre-test data are used to choose the appropriate study design and calculate the required sample size.

Adult↗
PubMed1991

Absence of sustained effects of acute fluoride exposure on cyclic AMP levels in the adult rat.

Previously published results from studies of the in vivo effects of fluoride on cyclic AMP are contradictory. Because of the important physiological role of cyclic AMP as a "second messenger" in numerous metabolic processes, it was important to clarify the effect of fluoride on cyclic AMP. This study was designed to monitor cyclic AMP levels in the plasma, liver and kidney of rats at intervals of 0.5, 4 and 24 hours following acute intraperitoneal or intubated treatment with a single dose of 15 mg fluoride/kg and to relate cyclic AMP levels to plasma and tissue fluoride concentrations determined at the same time.

Animals↗
PubMed1990

Evaluation of mutagenicity of restorative dental materials using the Ames Salmonella/microsome test.

Compounds of five commercially available dental material kits were examined for mutagenic potential by use of the Ames Salmonella/microsome test. Dimethyl sulfoxide (DMSO) was used as the solvent for all materials, except MONO-LOK2 Primer and Right-On Activator, which were dissolved in 95% ethanol. The Tenure, Fuji, and Gluma materials were initially screened at 2 mg (solids) or 2 microL (liquids) per plate, without S9 (Aroclor 1254-induced rat liver microsomes), and dose-response studies were conducted for those materials showing potential mutagenicity. The components of three dental kits, MONO-LOK2, Right-On, and Gluma, were further examined, both with and without S9 activation, at doses of 0.2, 4, 20, 100, 500, and 2500 micrograms (nL for liquid components) per plate. The data showed no mutagenic potential for the components of Fuji Glass Ionomer (Type III), Tenure Dentin Bonding System, and MONO-LOK2 kits, or Right-On Paste. However, Gluma 3, a component of the Gluma/Lumifor Bonding System, exhibited mutagenic activity in a dose-response manner. The mutagenicity of Gluma 3 was demonstrated in repeated experiments. Gluma 4 and the resin of the Gluma dental kit, as well as Right-On Activator, caused a slight increase in the number of revertants, and judgment regarding their mutagenicity could not be made conclusively. The results of this study indicate that some commercial dental materials may not have been adequately tested for mutagenicity, and that a reliable test program for evaluation of mutagenicity of dental materials is needed so that their safe use in dental practice can be ensured.

Aldehydes↗
PubMed1989

Genotoxic evaluation of chronic fluoride exposure: sister-chromatid exchange study.

As part of a continuing investigation, this study was conducted to examine the genotoxic effects of chronic exposure to sodium fluoride (NaF) in drinking water on the frequency of sister-chromatid exchange (SCE) in the bone-marrow cells of male Chinese hamsters. Animals at about 3 weeks of age were randomly assigned to 6 groups, each with at least 3 hamsters, and were maintained on a low fluoride diet (less than 0.2 ppm F) throughout the experiment. At 4 weeks of age, the animals in groups I-V began to receive drinking water containing fluoride at concentrations of 0, 1, 10, 50 and 75 ppm, respectively. Group VI was treated with cyclophosphamide and served as the positive control. The animals were sacrificed at 24 weeks of age by cervical dislocation. The humeri and plasma were analyzed for fluoride content, which was found to increase with the increase in fluoride concentration in drinking water. Slides of chromosomes from bone-marrow cells were prepared and blindly examined for the frequency of SCE. The mean scores of SCE for the hamsters receiving drinking water containing F concentrations up to 75 ppm for 21 weeks ranged from 4.28 to 6.28 per cell, and were not significantly different from those of the negative controls (4.60-5.44/cell). The results indicated that chronic fluoride exposure had no effect on the frequency of SCE in Chinese hamster bone-marrow cells under the conditions of the present investigation.

Animals↗
PubMed1989

Genotoxic evaluation of chronic fluoride exposure: micronucleus and sperm morphology studies.

The purpose of this study was to investigate the genotoxic effects of chronic fluoride exposure on mammalian cells in vivo by use of the mouse bone-marrow micronucleus test and the sperm morphology methodology. Mice of genotype B6C3F1 were obtained at weaning and maintained on a low-fluoride diet (less than 0.2 ppm F) ad libitum throughout the experiment. The animals were randomly assigned to seven groups and given fluoride (as sodium fluoride) in concentrations ranging from 1.0 to 75 ppm in the drinking water. Negative (distilled water) and positive (cyclophosphamide) controls were included. After a 21-week treatment period, the animals were killed by cervical dislocation, and blood was obtained by cardiac puncture. Slides of femur marrow cells were prepared and blindly examined for the frequency of micronucleated polychromatic erythrocytes (MN-PCE). Slides of sperm from the cauda epididymides of the male mice were also prepared and similarly examined for morphological abnormalities. Weight of the testes was recorded, and the plasma, humeri, testes, and carcasses were saved for fluoride analyses. Analyses of bone and plasma fluoride confirmed the effective absorption of fluoride following ingestion. The frequency of MN-PCE, the count of abnormal sperm, and the weight of the testes for mice chronically exposed to fluoride, in doses ranging from approximately 0.3 to 23 mg/kg/day, were not significantly different from those of the negative control animals. The results of this study support the view that fluoride has no genotoxic effects.

Animals↗
PubMed1988

Genotoxic effects of fluoride: a controversial issue.

Fluoride is an element which is widely distributed in our environment. Its cariostatic efficacy has been well documented, and numerous studies indicate that at a concentration of 1 ppm in water, fluoride is beneficial for caries prevention and does not appear to exacerbate any diseases. Currently, more than half the American population is consuming naturally or artificially fluoridated water and efforts are being made to increase this proportion significantly. In addition, the multiple use of fluoride for dental caries prevention is clearly increasing. It is a common practice to use fluoride in a variety of delivery systems, including dentifrices, mouthrinses, pediatric supplements, and professional or self-applied topical solutions or gels as well as dental restorative materials. These dental products may contain fluoride in concentrations as high as 12,300 ppm. Increasing exposure of the population to fluoride has raised questions about the safety of this measure and has established the need for objective reappraisal. In particular, interest has developed regarding the genotoxic effects of fluoride. Unfortunately, there is, at present, only a limited amount of information available concerning the potential genotoxic effects of fluoride, and the results that have been published are contradictory and often very confusing. A review of the literature clearly indicates the importance of, and necessity for, clarifying the conflicts and controversies regarding this important issue.

Animals↗
PubMed1987

Absence of mutagenic and antimutagenic activities of fluoride in Ames salmonella assays.

The mutagenicity of fluoride (as sodium fluoride, NaF) was investigated with Ames Salmonella/microsome assays in strains of TA97a, TA98, TA100, TA102 and TA1535. The concentrations of NaF tested ranged from 0.44 to 4421 micrograms/plate (0.1 to 1000 ppm F), both with and without microsome activation. In addition, the suggested antimutagenic effect of fluoride was evaluated with known mutagens at various concentrations of NaF (0.44-442.2 micrograms/plate, 0.1-100 ppm F). The data showed that NaF, in amounts from 0.44 to 442.2 micrograms/plate (0.1-100 ppm F), failed to significantly increase the number of the revertants over the number observed in the solvent (distilled deionized water) controls. Increases of NaF to, and beyond, 1100 micrograms/plate (250 ppm F) resulted in a toxic effect and a reduction of the revertants to various degrees among the strains. NaF in the presence of known mutagens did not significantly decrease the number of the revertants. The results of this study indicate that NaF does not have mutagenic or antimutagenic effects in the strains tested with Ames Salmonella assays.

Animals↗