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Biomedical subjects

G M Whitford

Publications and source records attributed to G M Whitford.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Fluoride flux in the rabbit CCD: a pH-dependent event.

We measured fluoride flux (JF; pmol.min-1.mm-1) in the isolated rabbit cortical collecting duct (CCD) to investigate the determining factors of JF. The perfusate contained 100 microM fluoride and the bath was fluoride-free. Osmotically-induced lumen-to-bath water flux did not affect JF. When perfusate pH was reduced from 7.4 to 6.1 and from 6.1 to 5.0, JF increased from 0.008 +/- 0.002 to 0.027 +/- 0.007 (P less than 0.01) and from 0.018 +/- 0.003 to 0.040 +/- 0.005 (P less than 0.01), respectively. Acetazolamide at 10(-4) M in the bath reduced JF slightly though not statistically. The anion-transport inhibitor, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), at 10(-4) M in the perfusate did not affect JF. Substitution of luminal chloride with gluconate failed to affect JF in tubules from normal rabbits or from rabbits treated with deoxycorticosterone which stimulates chloride-bicarbonate exchange in the CCD. JF showed no correlation with transepithelial voltage which ranged from +4 to -104 mV. We conclude that the luminal pH represents the primary determining factor influencing JF in the rabbit CCD, and fluoride does not use a chloride-mediated or a DIDS-inhibitory transport pathway.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Fluoride release from three glass ionomer materials and the effects of varnishing with or without finishing.

The release rates of fluoride from discs made from three glass ionomer products, Miracle Mix (MM), Ketac-Silver (KS) and Ketac-Bond (KB), into artificial saliva for 3 weeks were determined. The discs were either not varnished, varnished or varnished and finished. The release rates were not proportional to the fluoride concentrations of the products and were ordered: MM > KB > KS. The rates declined sharply as a function of time regardless of the product or treatment. Varnishing the discs caused a reduction of 61-76% depending on the product. Finishing the varnished discs produced a significant increase in the fluoride release from MM but had no effect on the release from KS or KB. In a separate study with MM, it was determined that the release rate of fluoride was inversely proportional to the powder: liquid ratio used to prepare the discs.

Cermet Cements↗
PubMed1991

Fluoride, calcium and phosphorus metabolism in the rat: comparison of 'natural ingredient' with semipurified diets.

Three groups of weanling female rats were fed different, commercially available, 'natural ingredient' diets containing 12, 28 or 45 parts/10(6) F, mainly as bone meal, for six weeks. Two other groups were fed a low-fluoride (0.76 parts/10(6)) semipurified diet. They received fluoride doses, either in the drinking water or by daily intraperitoneal injection, which were approximately equal to the average dose of the other three groups. Rats on the 'natural ingredient' diets ingested more food and water and excreted more faeces and urine, effects which were attributed to the higher amounts of dietary fibre, Na, K and Cl. Thus, at any given concentration of fluoride in the food or water, the level of fluoride ingestion and the ensuing effects would be influenced by the type of diet used. The values for fractional fluoride absorption (45-49%) and retention (38-47%) were similar among the groups given 'natural ingredient' diets. In the groups given semipurified diet, the corresponding values were about twice as high with the exception that fractional absorption was negative (-41%) in the injected group, which indicated net intestinal secretion of fluoride. Fluoride balances and tissue concentrations were highest in the groups fed the semipurified diet, even though the level of intake was not always higher. The fractional values for calcium and phosphorus absorption (41-51%) and retention (33-43%) were also similar among the groups given 'natural ingredient' diets. The corresponding values were about twice as high in the groups fed the semipurified diet. In terms of supporting maximum bone calcification, phosphorus absorption was marginal in two of the groups on the 'natural ingredient' diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1991

A comparative study of fluoride pharmacokinetics in five species.

This study was designed to quantitate and compare the major features of the short-term pharmacokinetics of fluoride--i.e., the plasma (Cp), renal (Cr), and extra-renal (Cer) clearances--in young adult dogs, cats, rabbits, rats, and hamsters. Plasma and urine samples were collected for seven h after the iv administration of fluoride (0.5 mg F/kg). Cp ranged from 3.5 to 8.6 mL/min/kg in the dog and hamster, respectively. Cr ranged from less than 1.5 mL/min/kg in the dog and rabbit to about 3.5 mL/min/kg in the rat and hamster. Cer ranged from 2.1 mL/min/kg in the dog to over 4.5 mL/min/kg in the cat, rabbit, and hamster. It was concluded that (1) there are major quantitative differences in the metabolic handling of fluoride among the five species, and that (2) Cp, Cr, and Cer values of the young adult dog, when factored for body weight, resemble those of the young adult human most closely.

Animals↗
PubMed1991

Fluoride reabsorption by nonionic diffusion in the distal nephron of the dog.

This study was done to test the hypothesis that fluoride reabsorption is extensive from the distal nephron, the major site for tubular fluid acidification, and to compare the distal nephron handling of fluoride and chloride. Ten stop-flow studies were done in five dogs anesthetized with pentobarbital. Urinary alkalinization was achieved by the intravenous infusion of sodium bicarbonate and acetazolamide or lithium chloride. Acidification was achieved by the infusion of sodium nitrate or sodium sulfate. The results indicate that the extent of fluoride reabsorption from the distal nephron is inversely correlated with urinary pH (P less than 0.001). When the urine was strongly acidified by the infusion of sodium sulfate, urine to plasma fluoride concentration ratios were less than 1.0, a finding not previously reported from studies of the renal handling of fluoride. The reabsorption of fluoride from the distal nephron was not correlated consistently with that of chloride. The results indicate that the distal nephron is an important site for the reabsorption of fluoride and they provide additional evidence that HF is the permeating moiety.

Absorption↗
PubMed1991

Fluoride balance and tissue concentrations: effect of dose frequency.

The possible effects of dose frequency on the bioavailability, balance and tissue levels of fluoride were determined using young adult rats. It was hypothesized that, because of the rapidly exchangeable pool of fluoride in calcified tissues, smaller and more frequent doses of fluoride would increase the retention of fluoride in the body. All groups were fed a low-fluoride, semi-purified diet throughout the six-week study. Group B received water with 25 ppm fluoride ad libitum. Groups C, D, and E received fluoride in amounts similar to that of group B but by ig intubation one or three times each day or by ip injection once each day. Group A received fluoride only in the food. Two 24-h fluoride intake and excretion determinations were made during each week. Plasma, enamel and femur epiphysis fluoride levels were determined at the end of the study. Compared with group B, the average fluoride absorption and balance values were 13% and 10% higher, respectively, in groups C, D and E. Plasma and calcified tissue fluoride levels were also slightly higher in the latter groups but, in general, the differences were not statistically significant. In the ip-injected group, the fecal excretion of fluoride was 96% greater than the amount ingested with the diet which indicated net intestinal secretion. It was concluded that, for a given level of intake, dose frequency has only minor effects on the absorption, balance and tissue levels of fluoride in the rat. The influence of the rapidly exchangeable calcified tissue fluoride pool on the general metabolism of the ion appears to be limited when intake occurs at least once each day.

Absorption↗
PubMed1990

Calcium-induced inhibition of taurine transport in brush-border membrane vesicles from rabbit small intestine.

The influence of Ca2+ on the activity of the taurine transport system was investigated in rabbit small intestinal brush-border membrane vesicles. Preincubation of the brush-border membrane vesicles with Ca2+ prepared by the Mg2(+)-aggregation method markedly decreased the NaCl gradient-dependent uptake of taurine in these vesicles. Uptake of glucose and alanine, both dependent on a Na+ gradient, were also decreased by Ca2(+)-treatment, but their reduction was very small compared with that of taurine uptake. The inhibitory effect of Ca2+ was dose- and time-dependent. The inhibition was reduced by the presence of ethylene glycol-bis(beta-amino ethyl ether)-N,N,N'-N'-tetraacetic acid during treatment of the membrane vesicles with Ca2+. Neomycin partially protected the taurine transporter activity from the Ca2(+)-induced inhibition, but indomethacin did not. 5-Nitro-2-(3-phenylpropylamino)benzoate, a Cl(-)-channel blocker, did not increase taurine uptake in the Ca2(+)-treated membrane vesicles. It is concluded that the Ca2(+)-induced inhibition of taurine uptake in rabbit intestinal brush-border membrane vesicles is not due to accelerated dissipation of the ion gradient driving forces across the membrane but rather to a direct effect on the transporter, most likely mediated by the activation of the membrane-bound phospholipase C.

Alanine↗
PubMed1990

Hydrolysis and transport of proline-containing peptides in renal brush-border membrane vesicles from dipeptidyl peptidase IV-positive and dipeptidyl peptidase IV-negative rat strains.

In this investigation, we have demonstrated that the renal brush-border membrane of Fischer 344 rats from the Japanese Charles River Inc. specifically lacks dipeptidyl peptidase IV (DPP IV) activity, whereas the renal brush-border membrane of Fischer 344 rats from three different sources within the United States possesses normal levels of DPP IV activity. Comparison of the brush-border proteins between Charles River (U.S.A.) Fischer 344 rats (DPP IV positive) and Japanese Charles River Fischer 344 rats (DPP IV negative) revealed that a protein band (Mr = 100,000), apparently identical with DPP IV, was absent in the membranes from Japanese Charles River Fischer 344 rats. We examined the handling of radiolabeled beta-casomorphin fragment 1-5 (Tyr-Pro-[3H]Phe-Pro-Gly), a specific substrate for DPP IV, in renal brush-border membrane vesicles isolated from DPP IV-positive and DPP IV-negative rats. Although the membrane vesicles from DPP IV-positive rats were able to hydrolyze the pentapeptide to di- and tripeptides with the subsequent active transport of these products via the H+ gradient-dependent peptide transport system, the membrane vesicles from DPP IV-negative rats failed to hydrolyze the pentapeptide and hence lacked the ability to transport the radiolabel actively from the parent peptide. The H+ gradient-dependent glycyl-sarcosine uptake and the Na+ gradient-dependent proline uptake, however, were normal in DPP IV-negative rats. Urine analysis revealed that the DPP IV-negative rats excreted proline- and hydroxyproline-containing peptides in significantly increased amounts in their urine compared with control rats. Furthermore, following intravenous administration of Tyr-Pro-Phe-Pro-NH2, a peptide that is exclusively hydrolyzed by DPP IV, urinary excretion of the peptide in the intact form was many-fold greater in DPP IV-negative rats than in control rats. These data provide conclusive evidence for the obligatory role of DPP IV in the renal handling of proline (and hydroxyproline)-containing peptides.

Animals↗
PubMed1990

Enamel and dentin fluoride levels and fluorosis following single fluoride doses: a nuclear microprobe study.

Female rats were given single intraperitoneal doses of fluoride (F) (0, 4, 7, or 14 mg F/kg body weight). Plasma F levels returned to predose values within 24 h. Incisors from animals killed 35 or 70 days after the F doses had been given were analyzed for mineralization defects by microradiography, and for F and P concentrations by nuclear microprobe. At 35 days, all F-injected rats had enamel fluorosis. At 70 days, by which time the incisors would have been renewed nearly twice, fluorosis was still evident in the 14 mg/kg body weight group. The enamel and dentin F concentrations at each time point were proportional to the administered F doses that had been given weeks earlier. The F concentrations at 35 days were similar to those found at 70 days. The results support the hypothesis that, following pulse loading, F can be mobilized from the bone adjacent to the enamel organ and result in local F concentrations sufficiently large to adversely affect amelogenesis.

Animals↗
PubMed1990

The physiological and toxicological characteristics of fluoride.

The metabolism and toxicity of fluoride are discussed with emphasis on new scientific findings. The gastric absorption, tissue distribution, and renal excretion of the ion are all influenced by the magnitude and direction of the pH gradient between adjacent body fluid compartments. This mechanism explains the asymmetric distribution of fluoride across cell membranes, and the manipulation of transmembrane pH gradients has proven efficacious in acute fluoride toxicity. The comparative metabolism and relative toxicities of ionic fluoride and monofluorophosphate are discussed. It is no longer certain that there is a difference between the acute toxic potentials of sodium fluoride and those of MFP. It is concluded that the "probably toxic dose" or PTD of fluoride--the dose which should trigger therapeutic intervention and hospitalization--is 5 mg/kg of body weight. As currently packaged, many dental products contain sufficient fluoride to exceed the PTD for young children. There is a need for additional research into the sources, effects, and fate of strongly bound or organic fluoride compounds. Attention is drawn to the fact that, while the metabolic characteristics and effects of fluoride in young and middle-aged adults have received considerable research attention, there is a paucity of such information for young children and the elderly. The increasing prevalence of dental fluorosis is addressed. It is concluded that nondietary sources of fluoride, mainly fluoride-containing dental products, are a major source of ingested fluoride. The article concludes with 12 recommendations for future research.

Absorption↗
PubMed1990

Environmental and physiological factors affecting dental fluorosis.

In addition to differences in fluoride intake and possibly to calcium deficiency or malnutrition, there are several factors which may account for individual differences in the occurrence of dental fluorosis. Disorders in acid-base balance affect the renal handling of fluoride such that, in acidosis, the excretion rate is diminished and, in alkalosis, the excretion rate is enhanced. Thus, any factor that can decrease urinary pH would be expected to increase the likelihood of dental fluorosis and vice versa. Results from studies with both rats and dogs have shown that acid-base disturbances per se, especially acidosis, adversely affect the mineralization of enamel in a manner that resembles fluorosis. It has been found that the retention and tissue levels of fluoride are increased by residence at high altitude. It has also been found that, in the absence of fluoride exposure, residence at high altitude per se can have a profound disruptive effect on amelogenesis which could be confused with fluorosis. The effects of diseases which lead to increases in urinary flow rate and water intake on the likelihood of the occurrence of dental fluorosis are also discussed.

Acid-Base Imbalance↗
PubMed1979

Fluoride tissue distribution: short-term kinetics.

The short-term distribution kinetics of 18F, with and without added carrier, were studied in 12 soft tissues and femur following intravenous administration in rats. The animals were killed in groups of four at 5, 10, 15, 20, 30, and 60 min after the dose. A tissue was judged to be kinetically homogeneous with plasma if an early and constant tissue water-to-plasma (T/P) 18F concentration ratio was established. In the carrier-free study, liver, heart, skin, fat, and kidney met this criterion. In the presence of carrier, four other tissues were added to this group. Brain, resting skeletal muscle, spleen, and femur did not achieve constant T/P values. The addition of carrier resulted in significantly lower T/P ratios in nine tissues. This was especially marked in femur. It is concluded that 1) none of the soft tissues studied strongly binds 18F; 2) most of these tissues are kinetically homogeneous with plasma; and 3) the presence of carrier fluoride can significantly influence the kinetic behavior and distribution of 18F. Finally, based on the current and previously reported 18F T/P ratios, and on reported intracellular-extracellular pH gradients, it is hypothesized that fluoride distribution in several soft tissues is determined by the diffusion equilibrium of HF, that is, by the magnitude of the transmembrane pH gradient.

Animals↗
PubMed1979

Plasma and developing enamel fluoride concentrations during chronic acid-base disturbances.

Mild acid-base disturbances were induced in rats for 30 days. These disturbances did not affect % ash of maxillary incisors or % P of the developing enamel from mandibular incisors. Total fluoride intake (food and water) among groups drinking fluoride-free water was constant. Nevertheless, average plasma and developing enamel fluroide concentrations were highest in the acidotic group and lowest in the alkalotic group. Among groups drinking water containing 50 ppm fluoride, total fluoride intake was highest by the alkalotic group and lowest by the acidotic group. Plasma and enamel fluoride concentrations, however, were highest in the acidotic group. It is concluded that plasma and developing enamel fluoride levels can be independent of, or inversely related to, fluoride intake.

Acid-Base Imbalance↗