Search PubMed⌕ Search

Biomedical subjects

G M Whitford

Publications and source records attributed to G M Whitford.

At least 19 recordsLinked to original sources
PubMed2001

Relating nickel-induced tissue inflammation to nickel release in vivo.

Nickel has a number of adverse biological effects that have made the use of nickel in biomedical implants controversial. Yet information about the distribution of nickel in tissues around nickel-containing implants is scarce. The purpose of the current study was to use a laser ablation technique, combined with inductively coupled mass spectroscopy, to assess the spatial distribution of nickel around nickel-containing implants in vivo. Polyethylene, pure nickel wire, or a nickel-containing alloy (Ni-Cr) were implanted subcutaneously into rats for 7 days. The tissues were analyzed for Ni content and inflammation at 1-mm intervals up to 5 mm away from the implants. The sham surgery sites and the polyethylene caused mild to moderate inflammation 1-2 mm from the implant site with no detectable nickel in the tissue. The nickel wire caused severe inflammation up to 5 mm away from the implant site with necrosis for 1 mm around the implant. Nickel concentrations reached 48 microg/g near the implants, falling exponentially to undetectable levels at 3-4 mm from the implants. The Ni-Cr wire caused inflammation equivalent to polyethylene, with less than 4 microg/g of nickel present in the tissue for 1-2 mm around the implants. The current study showed that the laser-ablation technique was well suited for the analysis of soft tissues for metal-ion content, and that the nickel distribution in tissues correlated well with overt tissue inflammation.

Alloys↗
PubMed1999

Effects of caffeine on fluoride, calcium and phosphorus metabolism and calcified tissues in the rat.

This 6-week study was designed to determine the effects of graded doses of caffeine intake (3, 25 or 100 mg/kg per day) on the metabolic balance and tissue concentrations of fluoride, calcium and phosphorus in Sprague-Dawley rats. Caffeine intake did not affect the absorption, urinary excretion or balance of fluoride, the plasma, bone or enamel concentrations of fluoride, nor the occurrence of incisor enamel fluorosis. Neither did it affect the metabolism of calcium or phosphorus except that the urinary excretion of calcium was increased. This effect, however, was not sufficient to influence significantly calcium balance. The ash content of the femur epiphysis and bone mineral content of the tibia were significantly reduced only in the group exposed to the highest dose of caffeine. These effects on bone were not significantly related to the balance of calcium or phosphorus. It was concluded that caffeine, even at an extremely high level of intake, has no detectable effect on the balance or tissue concentrations of fluoride, calcium or phosphorus in the rat.

Animals↗
PubMed1999

Fluoride in whole saliva, parotid ductal saliva and plasma in children.

The purpose was to investigate the relation between fluoride concentrations in whole saliva, parotid ductal saliva, and plasma in 5- to 10-year-old children (n = 17). Two stimulated whole-saliva samples were obtained from each child. Before the second sample was obtained, each child rinsed several times with a total of 100 ml of deionized water. Parotid saliva samples were obtained by use of a Lashley cup. Fluoride concentrations were determined by fluoride ion-specific electrode after diffusion with hexamethyldisiloxane. Rinsing with deionized water did not significantly reduce the fluoride concentration in whole saliva. The whole-saliva fluoride concentrations were not significantly related to those in plasma or parotid ductal saliva. Parotid fluoride concentrations, however, were significantly related to plasma fluoride concentrations (p < 0.0001) by a proportionality constant of 0.80. It was concluded that parotid salivary fluoride concentrations can be used to estimate plasma fluoride concentrations in 5- to 10-year-old children.

Child↗
PubMed1999

Effect of resin cure mode and fluoride content on bracket debonding.

Enamel decalcification around brackets is sometimes observed during and after orthodontic treatment. Reports in the literature suggest that the preventive advantage of fluoride-releasing adhesive resins may be compromised by an increased incidence of bond failure. The purpose of this study was to determine the effects on shear debonding of incorporating fluoride into the bracket bonding system. Another purpose was to determine the effect of polymerization mode on debonding. Orthodontic brackets were bonded to bovine enamel using one of three types of adhesive resin--no-mix, chemically cured, or light-cured--each formulated with and without fluoride. The teeth were stored in artificial saliva for 24 hours or 30 days and then debonded in shear. Data analysis was performed using ANOVA followed by post-hoc multiple comparison between group pairs. It was found that: (1) fluoride had either no effect or it increased the bond value; (2) the no-mix adhesive demonstrated the lowest bond value; (3) the duration of storage in artificial saliva had no effect on the bond value of the chemically cured and light-cured adhesives but did affect the no-mix adhesive; and (4) the no-mix adhesive released significantly less fluoride than the two other products. Thus, the presence of fluoride in the bonding adhesive does not reduce the force required to debond in shear, and chemically or light-cured adhesives provide consistently higher bond values over extended immersion times than the no-mix product.

Acrylic Resins↗
PubMed1999

Chronic fluoride ingestion decreases 45Ca uptake by rat kidney membranes.

High exposures to fluoride (F-) may occur in environments rich in F- from natural or industrial sources and from misuse of F--containing dental care products, particularly by children. Both acute and chronic exposures to elevated levels of F- have negative effects on several calcium-dependent processes, including kidney glomerular and tubular function. We examined the effect of chronic F- ingestion on ATP-dependent 45Ca uptake by rat kidney membrane vesicles to characterize the mechanism by which high F- alters Ca++ transport in the kidney. Twenty weanling female Sprague-Dawley rats were raised on low-F- (0.9 mg/L), semi-purified diet with a Ca++ concentration of 400 mg/100g diet. Rats were divided into four groups and were fed ad libitum deionized water containing F- at 0, 10, 50, or 150 mg/L added as NaF for 6 wk. This consumption produced plasma F- levels of <0.4, 2, 7, or 35 micromol/L, respectively. ATP-dependent 45Ca uptake was significantly lower in the 150 mg F-/L exposure group than in the 0 mg F-/L controls (P < 0.05). Studies with thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca++-pump, showed that the lower uptake was associated with significantly lower activities of both the plasma membrane Ca++-pump (P < 0.05, 150 mg F-/L group versus control) and endoplasmic reticulum Ca++-pump (P < 0.05 for both the 50 and 150 mg F-/L groups versus control). Slot blot analysis of kidney homogenates with specific Ca++-pump antibodies showed less (P < 0.05) endoplasmic reticulum Ca++-pump protein and plasma membrane Ca++-pump protein in all treatment groups than controls. Both Ca++-pumps are transport molecules of great importance in the regulation of Ca++ homeostasis. Our study suggests that chronic, high F- ingestion producing high plasma F- levels may occur in humans and may affect Ca++ homeostasis by increasing the turnover or breakdown or decreasing the expression of plasma membrane and endoplasmic reticulum Ca++-pump proteins.

Adenosine Triphosphate↗
PubMed1999

Fluoride metabolism and excretion in children.

This paper compares fluoride pharmacokinetics (plasma, renal, and extrarenal clearances) and metabolic balances in healthy infants or children with those in young or middle-aged adults. Regardless of age, the removal of fluoride from the intra- and extracellular body fluids occurs almost exclusively by uptake in calcified tissues and excretion in the urine. While there can be considerable differences among individuals, the rates at which fluoride is cleared from plasma by calcified tissues and the kidneys in adults are approximately equal. The calcified tissue clearance of fluoride from plasma in children is substantially higher than that by the kidneys. This is due to the greater surface area of the loosely organized crystallites in the developing calcified tissues during growth. Thus, the balance of fluoride (total intake minus total excretion) is typically higher in children than in adults, but it can be positive or negative at any age. Positive balance occurs when chronic fluoride intake is sufficient to prevent plasma concentrations from declining. When positive, the fluoride content of the calcified tissues, which contain more than 99 percent of the body's fluoride, tends to gradually increase. Negative balance, which indicates net mobilization of fluoride from calcified tissues, can occur when plasma concentrations decline due to a reduction in the level of fluoride intake.

Adolescent↗
PubMed1998

pH-dependent fluoride transport in intestinal brush border membrane vesicles.

Fluoride (F) absorption from the rat stomach and urinary bladder, hamster cheek pouch, and the renal tubules of several species are pH gradient-dependent. These observations led to the hypothesis that F crosses these epithelia in the form of the undissociated acid, HF. Several recent reports, however, have provided evidence that F absorption from the rat small intestine is insensitive to the lumenal pH. We report here our evidence that F uptake by rabbit intestinal brush border membrane vesicles (BBMV) occurred rapidly and with an overshoot only in the presence of an inward-directed proton gradient. In the absence of a proton gradient or in the presence of an outward-directed gradient, F uptake was slow and without an overshoot. In the presence of an inward-directed proton gradient, F uptake was partially inhibited by DIDS and DEP but not by diBAC. PCMBS inhibited F uptake by up to 83% in a dose-response manner. DiBAC appeared to reduce intravesicular pH slightly but the other reagents had no effect. When the uptake buffer contained chloride or nitrate, F uptake was partially inhibited compared to the mannitol or gluconate controls. It was concluded that F transport across the rabbit intestinal BBMV occurs via a carrier-mediated process which may involve cotransport of F with H+ or exchange of F with OH-. The inhibitory effects of DIDS, DEP and PCMBS may occur by affecting this carrier-mediated transport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Determinants and mechanisms of enamel fluorosis.

Enamel fluorosis occurs when fluoride concentrations in or in the vicinity of the forming enamel are excessive during its pre-eruptive development. Fluoride concentrations in plasma, enamel and other tissues reflect the difference between intake and excretion, i.e. fluoride balance. In addition to the diet, modern sources of ingested fluoride include a variety of dental products, some of which have been identified as risk factors for fluorosis. Fluoride absorption is inversely related to dietary calcium which, at high concentrations, may cause net fluoride secretion into the gastrointestinal tract. The excretion of absorbed fluoride occurs almost exclusively via the kidneys, a process which is directly related to urinary pH. Thus, fluoride balance and tissue concentrations and the risk of fluorosis are increased by factors such as high protein diets, residence at high altitude, and certain metabolic and respiratory disorders that decrease pH. Factors that increase urinary pH and decrease the balance of fluoride include vegetarian diets, certain drugs and some other medical conditions. Although several other fluoride-induced effects might be involved in the aetiology of fluorosis, it now appears that inhibition of enzymatic degradation of amelogenins, which may delay their removal from the developing enamel and impair crystal growth, may be of critical importance. In addition to the effects of fluoride, disturbances in enamel formation that can be confused with fluorosis are caused by chronic acidosis and hypoxia independently of the level of fluoride exposure.

Acidosis↗
PubMed1997

Effects of fluoride on structure and function of canine gastric mucosa.

These studies were done to determine the effects of fluoride (F) on the structure and function of the canine gastric mucosa and the possible protective effects of 16,16-dimethyl-prostaglandin E2 (dmPGE2). A portion of the stomach with its vascular supply intact was mounted in a two-compartment chamber, one side of which contained a control solution. Minor effects were caused by exposure to 1 mmol/liter F. Both 5 and 10 mmol/liter F caused marked increases in the fluxes of water and Na, K, and H ions; mucus secretion; and tissue swelling and redness. The extent of these changes did not increase appreciably upon exposure to 50 or 100 mmol/liter F. Histological findings included marked thinning of the surface cell layer, reduced uptake of PAS stain, localized exfoliation and necrosis of surface cells, acute gastritis, and edema. It was concluded that: (1) the threshold F concentration for effects on the structure and function of the gastric mucosa was approximately 1 mmol/liter; (2) the maximum or near-maximum effects were caused by 10 mmol/liter F; (3) the effects persisted for at least 6 hr after the exposure; and (4) dmPGE2 (0.5 microg/ml) did not attenuate the effects induced by F.

16,16-Dimethylprostaglandin E2↗
PubMed1995

A physiologically based pharmacokinetic model for fluoride uptake by bone.

A sex-specific, physiologically based pharmacokinetic (pbpk) model has been developed to describe the absorption, distribution, and elimination of fluorides in rats and humans. Growth curves generated by plotting mean body weights (kg) against age (weeks or years) are included in the simulation model to allow the integration of chronic fluoride exposure from birth to old age. The model incorporates age and body weight dependence of the physiological processes that control the uptake of fluoride by bone and the elimination of fluoride by the kidneys. Six compartments make up the model. These are lung, liver, kidney, bone, and slowly and rapidly perfused compartments. The model also includes two bone subcompartments: a small, flow-limited, rapidly exchangeable surface bone compartment and a bulk virtually nonexchangeable inner bone compartment. The inner bone compartment contains nearly all of the whole body content of fluoride, which, in the longer time frame, may be mobilized through the process of bone modeling and remodeling. The model has been validated by comparing the model predictions with experimental data gathered in rats and humans after drinking water and dietary ingestion of fluoride. This physiological model description of absorption, distribution, and elimination of fluoride from the body permits the analysis of the combined effect of ingesting and inhaling fluorides on the target organ, bone. Estimates of fluoride concentrations in bone are calculated and related to chronic fluoride toxicity. The model is thus useful for predicting some of the long-term metabolic features and tissue concentrations of fluoride that may be of value in understanding positive or negative effects of fluoride on human health. In addition, the pbpk model provides a basis for across-species extrapolation of the effective fluoride dose at the target tissue, bone, in the assessment of risk from different exposure conditions.

Adult↗
PubMed1995

Fluorosis-like effects of acidosis, but not NH+4, on rat incisor enamel.

Previous studies have shown that chronic acidosis induced by NH4Cl is associated with disturbances in enamel mineralization that resemble severe fluorosis and increased fluoride concentrations in both soft and hard tissues. It has not been shown whether these effects are due to acidosis per se or exposure to high levels of NH+4. This 42-day study with rats fed a low-fluoride diet was done to identify the etiological factor. Two control groups received deionized water or water containing NaCl. Two groups received NH+4-containing compounds that did not produce acidosis (NH4HCO3 or HN4 acetate). Two other groups were rendered acidotic by exposure to NH4Cl in the drinking water (metabolic acidosis) or to an atmosphere containing 10% CO2 (respiratory acidosis). The femur epiphysial fluoride concentrations were elevated in the NH4Cl and NH4 acetate groups, and the magnesium concentrations were elevated in the groups exposed to NH+4 compounds and in the 10% CO2 group. Microradiographic analysis revealed severe disturbances in the mineralization pattern of incisor enamel in both acidotic groups, but normal enamel in the other groups. Enamel fluoride and magnesium concentrations were highest in the acidotic groups. The enamel fluoride concentrations were low (8-14 ppm) and not regarded as the cause of the defective mineralization. It was concluded that the effects on structure and composition of enamel were due to acidosis and not to exposure to high levels of NH+4.

Acidosis↗
PubMed1994

Acute fluoride poisoning from a public water system.

BACKGROUND: Acute fluoride poisoning produces a clinical syndrome characterized by nausea, vomiting, diarrhea, abdominal pain, and paresthesias. In May 1992, excess fluoride in one of two public water systems serving a village in Alaska caused an outbreak of acute fluoride poisoning. METHODS: We surveyed residents, measured their urinary fluoride concentrations, and analyzed their serum-chemistry profiles. A case of fluoride poisoning was defined as an illness consisting of nausea, vomiting, diarrhea, abdominal pain, or numbness or tingling of the face or extremities that began between May 21 and 23. RESULTS: Among 47 residents studied who drank water obtained on May 21, 22, or 23 from the implicated well, 43 (91 percent) had an illness that met the case definition, as compared with only 6 of 21 residents (29 percent) who drank water obtained from the implicated well at other times and 2 of 94 residents (2 percent) served by the other water system. We estimated that 296 people were poisoned; 1 person died. Four to five days after the outbreak, 10 of the 25 case patients who were tested, but none of the 15 control subjects, had elevated urinary fluoride concentrations. The case patients had elevated serum fluoride concentrations and other abnormalities consistent with fluoride poisoning, such as elevated serum lactate dehydrogenase and aspartate aminotransferase concentrations. The fluoride concentration of a water sample from the implicated well was 150 mg per liter, and that of a sample from the other system was 1.1 mg per liter. Failure to monitor and respond appropriately to elevated fluoride concentrations, an unreliable control system, and a mechanism that allowed fluoride concentrate to enter the well led to this outbreak. CONCLUSIONS: Inspection of public water systems and monitoring of fluoride concentrations are needed to prevent outbreaks of fluoride poisoning.

Adolescent↗
PubMed1994

Effects of plasma fluoride and dietary calcium concentrations on GI absorption and secretion of fluoride in the rat.

This 30-day balance study with weanling rats was designed to determine the effects of plasma fluoride and dietary calcium concentration and their interaction on the absorption, balance, and tissue concentrations of fluoride. The three major groups differed according to the total exposure and plasma concentrations of fluoride. One group received fluoride only in the diet and the other two received additional fluoride by continuous infusion from miniosmotic pumps implanted S.C. Each group was divided into two subgroups with dietary calcium concentrations of 0.4% or 1.4%. Fluoride intake with the diet did not differ among the groups. Fecal fluoride excretion was directly related to plasma fluoride concentration. The absorption and balance of dietary fluoride were inversely related to plasma fluoride concentration. These effects were greatest in the groups fed the 1.4% calcium diet. The interactions of plasma fluoride and dietary calcium on these variables were highly significant (P < 0.0001). The balance of dietary fluoride was negative in the four groups that received additional fluoride by infusion. In the two groups that received fluoride only in the diet, the plasma and bone fluoride concentrations were 41% and 59% lower, respectively, in the 1.4% dietary calcium group. The findings indicate that net fluoride secretion into the GI tract can occur when plasma fluoride concentrations and calcium intake are elevated. They suggest that elevated plasma fluoride levels and calcium intake are factors that may diminish the effect of oral fluoride treatment in osteoporotic patients.

Animals↗
PubMed1994

Effect of artificial saliva and calcium on fluoride output of controlled-release devices.

The purpose of this in vitro study was to assess the effect of graded concentrations of calcium in artificial saliva on the output of fluoride from HEMA/MMA controlled-release devices. After the initial release rates were determined in deionized water, the devices were assigned to five groups. The devices of one group remained in deionized water throughout the 19-day study while those of the other groups were placed in artificial saliva containing 0, 4.5, 8.0, or 12.0 mg% calcium on days 4-13. Ten devices of each group were placed in deionized water again on days 14-17 and then in 0.1 mol/l HCl on days 18-19. The five devices of each group that were not placed in deoinized water on day 14 were inspected for surface crystals and then placed in 1 mol/l KOH for 2 days. The fluoride release rates in artificial saliva were reduced by 71-90% and in proportion to the calcium concentration. The release rates in deionized water (days 14-17) approached the baseline values; they exceeded baseline rates by 13-49% while in HCl. The fluoride release rates did not differ among the groups while in KOH, but calcium output was directly related to the calcium concentration of the artificial saliva. The results indicate that fluoride release from HEMA/MMA devices is markedly reduced in artificial saliva and that the reduction is proportional to the concentration of calcium.

Calcium↗
PubMed1994

Lack of significant effect of coffee and caffeine on fluoride metabolism in rats.

It has been reported that rat plasma fluoride (F) concentrations are higher by up to 100% when F is administered ig in coffee or a caffeine solution compared with when it is administered in water. It was hypothesized that the consumption of caffeinated beverages has contributed to the prevalence of dental fluorosis. The present studies were done to determine the physiological mechanisms for these effects. For approximately 2 h after F was administered in coffee, plasma F concentrations were higher than when administered in water, decaffeinated coffee, or a caffeine solution (3 mg/kg), but the intergroup differences were small and generally not statistically significant. The 4-hour plasma AUC values did not differ with statistical significance. There were no differences among the groups in the renal or extrarenal (skeletal) clearances of F, which suggested that the higher plasma F concentrations in the coffee groups may have been due to a slight and transient increase in absorption rate. The possibility that caffeine per se might elevate endogenous plasma F and calcium concentrations was excluded after caffeine (25 mg/kg) ig without F was given. In addition, the renal excretion, clearance, and fractional renal clearance of calcium did not differ among the groups. The results indicated that decaffeinated coffee and caffeine had no effect on F metabolism, whereas caffeinated coffee appeared to increase the initial absorption rate but not the 4-hour bio-availability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Intake and metabolism of fluoride.

The purpose of this paper is to discuss the major factors that determine the body burden of inorganic fluoride. Fluoride intake 25 or more years ago was determined mainly by measurement of the concentration of the ion in the drinking water supply. This is not necessarily true today because of ingestion from fluoride-containing dental products, the "halo effect", the consumption of bottled water, and the use of water purification systems in the home. Therefore, the concentration of fluoride in drinking water may not be a reliable indicator of previous intake. Under most conditions, fluoride is rapidly and extensively absorbed from the gastrointestinal tract. The rate of gastric absorption is inversely related to the pH of the gastric contents. Overall absorption is reduced by calcium and certain other cations and by elevated plasma fluoride levels. Fluoride removal from plasma occurs by calcified tissue uptake and urinary excretion. About 99% of the body burden of fluoride is associated with calcified tissues, and most of it is not exchangeable. In general, the clearance of fluoride from plasma by the skeleton is inversely related to the stage of skeletal development. Skeletal uptake, however, can be positive or negative, depending on the level of fluoride intake, hormonal status, and other factors. Dentin fluoride concentrations tend to increase throughout life and appear to be similar to those in bone. Research to determine whether dentin is a reliable biomarker for the body burden of fluoride is recommended. The renal clearance of fluoride is high compared with other halogens. It is directly related to urinary pH. Factors that acidify the urine increase the retention of fluoride and vice versa. The renal clearance of fluoride decreases and tissue levels increase when the glomerular filtration rate is depressed on a chronic basis.

Animals↗
PubMed1992

The effects of protein deficiency and fluoride on bone mineral content of rat tibia.

This study examined the effects of chronic protein deficiency and fluoride administration (10 mg/kg/day), separately or in combination, on rat tibia properties. Protein deficiency increased the bone fluoride concentration and reduced the bone mineral content (BMC) especially at the proximal or growing end which contains mainly cancellous bone. Fluoride administration also reduced BMC, but to a lesser extent, and it resulted in proximal tibia fluoride concentrations that were nearly twice those of the distal tibia. The interaction between fluoride administration and the protein content of the diet on BMC was nonsignificant, suggesting that the effects were additive, not multiplicative or synergistic. Fluoride administration, but not protein deficiency, increased bone magnesium levels. It is hypothesized that the reduction in BMC in the areas where the fluoride concentrations were the highest was due to a localized toxic effect of fluoride.

Absorptiometry, Photon↗