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PubMed1993

Pathogenesis of cholesteryl lipidosis of adrenocortical and ovarian interstitial cells in F344 rats caused by tricresyl phosphate and butylated triphenyl phosphate.

Triaryl phosphates including tricresyl phosphate (TCP) and butylated triphenyl phosphate (BTP) are organophosphates used in the commercial manufacture of plastics, lubricants, and hydraulic fluids. Rat steroidogenic tissues such as adrenocortical (AC), ovarian interstitial (OI), and Leydig cells use an intracellular pathway to store cholesterol (substrate for biosynthesis of steroid hormones) as cholesteryl ester (CE). This pathway and the pathway for uptake of serum cholesterol are less used in Leydig cells of the adult male rat, resulting in a lower CE pool. BTP and TCP caused cholesteryl lipidosis in steroid hormone-synthesizing AC and OI, but not Leydig cells in the adult rat. The objectives of this study were to determine if the administration of triaryl phosphate fluids caused a defect in the cholesterol storage pathway of AC and OI cells and to determine the mechanism of action. Female rats received daily oral doses of 0 or 0.4 g/kg TCP in sesame oil vehicle or 1.7 g/kg neat BTP for 40 days. Adrenal glands from both treatment groups and ovaries from TCP-treated rats were heavier than controls. Microscopic and biochemical studies revealed cholesteryl lipidosis composed of CE in the adrenal glands and ovaries in BTP- and TCP-treated rats with the latter group affected most severely. The activity of neutral CE hydrolase (nCEH), an enzyme that converts CE to cholesterol in the uptake and storage pathways, also was inhibited most in the TCP-treated group (97% inhibition compared to that of control). The activity of acyl coenzyme A:cholesterol acyl transferase, an enzyme that esterifies cholesterol to make CE, was depressed 27% compared to that of control adrenal glands of the TCP group, resulting in elevated intracellular cholesterol levels in AC cells. An inhibition of nCEH in the storage and uptake pathways by triaryl phosphates most likely resulted in the striking accumulation of CE in cytoplasmic lipid droplets of AC and OI cells in F344 rats.

Adrenal Cortex Diseases↗
PubMed1996

The effects of exposure route on DNA adduct formation and cellular proliferation by 1,2,3-trichloropropane.

1,2,3-Trichloropropane (TCP) induces high incidences of tumors at multiple sites in mice and rats when administered chronically by gavage. The animal tumor data are being used to predict human risk from potential exposure to TCP in drinking water. Risk assessment may be affected by differences in the route of exposure. Gavage administration, which results in high bolus concentrations compared to drinking water exposure, may quantitatively affect toxicokinetics, cytotoxicity, and genotoxicity. We have examined the effects of TCP exposure by the two routes on the formation of DNA adducts and the induction of cellular proliferation. Male B6C3F1 mice were administered [14C]TCP for 1 week by gavage or in drinking water at the low dose (6 mg/kg) used in the NTP carcinogenesis bioassay. Two target organs (forestomach and liver) and two nontarget organs (glandular stomach and kidney) were examined for DNA adduct formation. Adducts were hydrolyzed from DNA, isolated by HPLC, and quantitated by measuring HPLC fractions for radioactivity. In the forestomach, liver, and kidney, gavage administration of TCP resulted in 1.4-to 2.4-fold greater yields of the major DNA adduct, previously identified as S-[1-(hydroxymethyl)-2-(N7-guanyl)ethyl]glutathione. Significant differences in cell proliferation, as determined by incorporation of bromodeoxyuridine into DNA, were also observed for the two routes. Gavage administration of TCP for 2 weeks resulted in up to a threefold greater cell proliferation rate relative to administration in drinking water. Our findings of exposure-related differences in TCP-induced DNA adduct formation and cell proliferation suggest that a risk assessment based on the existing gavage study may overestimate human risk.

Administration, Oral↗
PubMed1997

Stabilization of an inserted tricalcium phosphate spacer enhances the healing of a segmental tibial defect in sheep.

The effect of inserting a tricalcium phosphate (TCP) spacer stabilized by a rigid or non-rigid fixation technique on the healing of segmental tibial defects of critical size was established. The osteotomized tibiae, 11 with and 8 without TCP spacers, were fixed by an external circular device in 11 mature sheep and by plates in 8 mature sheep, respectively. Healing was evaluated roentgenographically 16 weeks after the operation. Compared with the defects without TCP spacers, enhanced stability and healing were observed in the defects with TCP spacers under an identical external fixation. Furthermore, a significantly higher incidence of healing was obtained with plate fixation than with external device fixation in the TCP-implanted defects (P < 0.04). An abundant bridging callus was roentgenograpically demonstrated in most of the healed defects, but none in the unhealed defects. The TCP spacer with its mechanical integrity enhances the stability of external fixation, and the stable immobilization provided by rigid fixation is essential for osteoconduction of an inserted TCP spacer in the healing of segmental diaphyseal defects in sheep.

Animals↗
PubMed1990

The absorption of tricalcium phosphate and its acute metabolic effects.

The use of calcium (Ca) supplements by postmenopausal women is growing rapidly. A commercial preparation of tricalcium phosphate (TCP) is available in the USA. Depending on the relative absorption of Ca versus phosphate, a rise in serum phosphorus (P) could stimulate parathyroid hormone (iPTH) secretion. We therefore compared Ca absorption and the metabolic responses following TCP to that of Ca carbonate (CC) on separate occasions in each of 10 women, aged 22-40 years. The subjects were fasted overnight for 12 hours while good hydration was maintained. Following a 2-hour baseline-urine collection, 1200 mg calcium (as CC or TCP) was ingested and two 2-hour postload urine collections were made. Blood was drawn at 1, 2, and 4 hours after the Ca load. Serum (S) and urine (U) Ca, P, and creatinine, and U cyclic AMP (cAMP) were determined. iPTH levels following TCP were also measured. Ca absorption was determined by the postload rise in Uca above baseline. Uca excretion increased significantly and was accompanied by significant rises in Sca after both preparations. Following TCP, S and U phosphorus increased. Urinary cAMP did not change after either preparation, and iPTH levels fell after oral TCP. We conclude that Ca taken as TCP is absorbed adequately and, thus, despite a rise in the S phosphorus level does not stimulate parathyroid activity.

Administration, Oral↗
PubMed2001

The effects of radiotherapy treatment uncertainties on the delivered dose distribution and tumour control probability.

Uncertainty in the precise quantity of radiation dose delivered to tumours in external beam radiotherapy is present due to many factors, and can result in either spatially uniform (Gaussian) or spatially non-uniform dose errors. These dose errors are incorporated into the calculation of tumour control probability (TCP) and produce a distribution of possible TCP values over a population. We also study the effect of inter-patient cell sensitivity heterogeneity on the population distribution of patient TCPs. This study aims to investigate the relative importance of these three uncertainties (spatially uniform dose uncertainty, spatially non-uniform dose uncertainty, and inter-patient cell sensitivity heterogeneity) on the delivered dose and TCP distribution following a typical course of fractionated external beam radiotherapy. The dose distributions used for patient treatments are modelled in one dimension. Geometric positioning uncertainties during and before treatment are considered as shifts of a pre-calculated dose distribution. Following the simulation of a population of patients, distributions of dose across the patient population are used to calculate mean treatment dose, standard deviation in mean treatment dose, mean TCP, standard deviation in TCP, and TCP mode. These parameters are calculated with each of the three uncertainties included separately. The calculations show that the dose errors in the tumour volume are dominated by the spatially uniform component of dose uncertainty. This could be related to machine specific parameters, such as linear accelerator calibration. TCP calculation is affected dramatically by inter-patient variation in the cell sensitivity and to a lesser extent by the spatially uniform dose errors. The positioning errors with the 1.5 cm margins used cause dose uncertainty outside the tumour volume and have a small effect on mean treatment dose (in the tumour volume) and tumour control.

Humans↗
PubMed2002

Pharmacokinetic profile and placental transfer of a single intravenous injection of [(14)C]chlorpyrifos in pregnant rats.

The pharmacokinetics and placental transfer of a single intravenous dose of 5.0 mg/kg (10 micro Ci/kg) ring-labeled [(14)C]chlorpyrifos were investigated in pregnant Sprague-Dawley rats at 11-13 days of gestation. Three rats were killed at 5, 15 or 30 min, or 1, 2, 4, 8, 12, 18, 24, 36, 48, 72 or 96 h after dosing. Radioactivity and 3,5,6-trichloropyridinol (TCP) were detected in all tissues 5 min after dosing. Chlorpyrifos was only found in maternal plasma and liver. Peak maternal plasma concentration of radioactivity ( micro g chlorpyrifos equivalents/ml) was 157 at 5 min, compared with 1.9 for fetal plasma at 15 min. The maximum concentrations of radioactivity ( micro g chlorpyrifos equivalents/g), detected in most tissues within 12 h of dosing, were, in descending order: liver (30), brain (29), placenta (21), and fetus (2). All peaks occurred at 5 min except for fetus and fetal plasma, which were at 15 min. TCP was detected by HPLC as the major compound identified in plasma and tissues. The maximum concentration detected was in plasma, at 12.4 micro g/ml, and for the following tissues was: liver 4.3 ng/g fresh tissue, fetus 4 ng/g, placenta 2.97 ng/g, brain 1.68 ng/g, and fetal plasma 0.52 ng/g. All TCP peaks occurred at 5 min except for fetus at 30 min and fetal plasma at 15 min. Parent chlorpyrifos was detected in maternal plasma and liver at maximum concentrations of 5.1 micro g/ml and 0.40 micro g/g, respectively, at 5 min. Chlorpyrifos was detectable in maternal plasma up to 36 h after dosing, and in liver up to 24 h after dosing. Pharmacokinetic analysis best described radioactivity, chlorpyrifos, and TCP as disappearing biexponentially from plasma and tissues. The terminal elimination half-lives of radioactivity, chlorpyrifos and TCP from maternal plasma were 16, 18, and 16 h, respectively. The results indicate that (1). chlorpyrifos undergoes a rapid metabolism to its major metabolites (TCP); (2). chlorpyrifos and its metabolites are distributed to all maternal and fetal tissues and plasma; and (3). the elimination of chlorpyrifos and TCP is slow, with redistribution from lipid stores a likely determinant of elimination rates.

Animals↗
PubMed2002

Aerobic degradation of 2,4,6-trichlorophenol by a microbial consortium - selection and characterization of microbial consortium.

A microbial consortium that efficiently degrades 2,4,6-TCP (2,4,6-trichlorophenol), as the sole source of carbon and energy under aerobic conditions was selected from municipal activated sludge. Six bacterial strains, designated S(1), S(2), S(3), S(4), S(5) and S(6), were isolated from the selected consortium and five were identified as Sphingomonas paucimobilis (S(2), S(3)), Burkholderia cepacia(S(4)), Chryseomonas luteola (S(5)) and Vibrio metschnikovii (S(6)). After prolonged cultivation followed by successive transfers, the consortium's degradation ability was improved and reached a specific degradation rate of 34 mg 2,4,6-TCP g(-1) dry weight h(-1) (about 51 mg 2,4,6-TCP g(-1) cell protein h(-1)). The soluble chemical oxygen demand, chloride and oxygen uptake balance data clearly indicate the complete dechlorination and mineralization of 2,4,6-TCP. The consortium's activity was not inhibited by 2,4,6-TCP concentrations <or=400 mg l(-1). The highest specific growth rate (micro(max) of 0.01 h(-1)) was achieved at 2,4,6-TCP concentration <or=200 mg l(-1), and the inhibition constant ( K(i)) was 610 mg l(-1) according to the Haldane inhibition kinetic model. An inoculum size up to 120 mg l(-1) cell dry weight is desirable in order to avoid a lag phase and to allow faster degradation of 2,4,6-TCP.

Aerobiosis↗
PubMed2002

Adaptation of the white-rot basidiomycete Panus tigrinus for transformation of high concentrations of chlorophenols.

During feed-batch cultivation of the white-rot fungus Panus tigrinus in a 5-l bioreactor on N-limited medium, 100, 200, 500, 1,000 and 2,000 mg 2,4,6-trichlorophenol (2,4,6-TCP) l(-1) were added sequentially after 90% removal of the previous portion of the toxicant. The addition of 500 mg 2,4,6-TCP l(-1) without preliminary adaptation killed the culture. The addition of 300 mg 2,4,6-TCP l(-1) without prior adaptation resulted in its slower removal than removal of 2,000 mg 2,4,6-TCP l(-1) by this adapted culture. After adaptation of P. tigrinus to 2,4,6-TCP in a 72-l bioreactor, the mixture of 2,4-dichlorophenol, 2,4,6-TCP, and pentachlorophenol, each at 500 mg x l(-1), was totally removed over 3 weeks. No lignin peroxidase activity was found in the course of cultivation of the fungus. Laccase activity was suppressed by addition of 2,4,6-TCP. Mn-peroxidase was found to be responsible for transformation of the chlorophenols. As final products of the process, several newly formed aromatic polymers, both chlorinated and non-chlorinated, were found in the culture liquid.

Adaptation, Physiological↗
PubMed1997

Use of immobilized bacteria to treat industrial wastewater containing a chlorinated pyridinol.

Pseudomonas sp. strain M285 immobilized on diatomaceous earth beads was used to remove 3,5,6-trichloro-2-pyridinol (TCP) from industrial wastewater. Batch studies showed that immobilized Pseudomonas sp. strain M285 mineralized [2,6-14C]TCP rapidly; about 75% of the initial radioactivity was recovered as 14CO2. Transformation of TCP was inhibited by high concentrations of salt, and addition of osmoprotectants (proline and betaine at 1 mM) did not reduce the adverse effect of salt. TCP-containing wastewater (60-140 mg/l) was passed through columns containing immobilized Pseudomonas sp. strain M285 at increasing flow rates and increasing TCP concentrations; TCP removal of 80%-100% was achieved. Addition of nutrients, such as glucose and yeast extract, retarded TCP degradation. Growing cell cultures were found to be better inocula for immobilization than resting cells.

Betaine↗
PubMed2001

Porous tricalcium phosphate and transforming growth factor used for anterior spine surgery.

Harvesting autologous bone graft from the iliac crest is associated with considerable secondary morbidity. Bone graft substitutes such as porous ceramics are increasingly used for spinal surgery. This paper presents the results of an animal study in which beta-tricalcium phosphate (beta-TCP) bone substitutes were used for anterior spinal surgery in sheep and baboons. The presented baboon study also investigated the effect of impregnating the ceramic material with transforming growth factor (TGF). In the first study, using the sheep model, a stand-alone instrumented anterior fusion was performed. The animals were randomized into three treatment groups: autologous bone, beta-TCP granules, and sham group. The results were analyzed biomechanically and histologically at three survival intervals: 8, 16 and 32 weeks. An additional animal group was added later, with ceramic pre-filled implants. In the second study, a baboon model was used to assess the osteointegration of a 15-mm-diameter porous beta-TCP block into the vertebral body. The experiment was partially motivated by a new surgical procedure proposed for local bone graft harvest. Three treatment groups were used: beta-TCP plug, beta-TCP plug impregnated with TGF-beta3, and a sham group with empty defect. The evaluation for all animals included computer tomograms at 3 and 6 months, as well as histology at 6 months. In the sheep model, the mechanical evaluation failed to demonstrate differences between treatment groups. This was because massive anterior bone bridges formed in almost all the animals, masking the effects of individual treatments. Histologically, beta-TCP was shown to be a good osteoconductor. While multiple signs of implant micromotion were documented, pre-filling the cages markedly improved the histological fusion outcomes. In the baboon study, the beta-TCP plugs were completely osteointegrated at 6 months. For the group that used ceramic plugs impregnated with TGF-beta3, no incremental advantage was seen as a result of this particular application. However, TGF-beta3 is a potent growth factor at a very low dose. Not only does it speed up the ceramic material resorption, but it is also responsible for massive regional new bone formation. More experiments are required to better understand the biological effects of this growth factor in relation to bone formation, and to be able to take clinical advantage of them.

Animals↗
PubMed1992

In vitro metabolism and bioactivation of 1,2,3-trichloropropane.

In vitro studies using rat and human hepatic microsomes have shown that the halogenated hydrocarbon 1,2,3-trichloropropane (TCP) is bioactivated to the direct acting mutagen 1,3-dichloroacetone (DCA). The presence of DCA in microsomal incubations was confirmed by gas chromatography-mass spectrometry. DCA formation was totally dependent on the presence of NADPH. The rate of DCA formation using rat and human microsomes was 0.268 +/- 0.029 and 0.026 +/- 0.006 nmol/min/mg protein +/- SE, respectively. When hepatic microsomes were isolated from rats pretreated with the cytochrome P-450 inducers, phenobarbital, and dexamethasone, 24- and 2.5-fold increases, respectively, in the rate of DCA production, were observed. Pretreatment with beta-naphthoflavone resulted in a 50% inhibition in DCA formation. The inhibitors of cytochromes P-450, SKF 525-A and 1-aminobenzotriazol, produced 85 and 70% inhibitions of DCA formation, respectively. When alcohol dehydrogenase and NADH were added to microsomal incubations, two TCP-related alcohols, 1,3-dichloro-2-propanol and 2,3-dichloropropanol, were formed. These alcohols are products of the initial microsomal metabolites, DCA and 2,3-dichloropropanal. [14C]TCP equivalents bound covalently to rat hepatic microsomal protein. This binding was increased 8-fold when hepatic microsomes from phenobarbital pretreated rats were used. The addition of either glutathione or N-acetylcysteine to the incubations completely inhibited this binding. In the presence of N-acetylcysteine, 1,3-(2-propanone)-bis-S-(N-acetylcysteine) (PDM) was the only N-acetylcysteine conjugate detected. It represented 87% of TCP microsomal metabolism. The formation of PDM implicates DCA as the major microsomal protein-binding metabolite of TCP. The formation of DCA, a direct-acting mutagen, may be responsible for the mutagenicity of TCP in systems using rat hepatic microsomes. Its role in the tumorigenicity and carcinogenicity of TCP remains to be established.

Acetone↗
PubMed1995

Effects of treatment setup variation on beam's eye view dosimetry for radiation therapy using the multileaf collimator vs. the cerrobend block.

PURPOSE: The purpose of this study is to quantify and compare retrospectively the effects of treatment setup variation on beam's eye view (BEV) dosimetry for radiation therapy using a multileaf collimator (MLC) vs. cerrobend block. METHODS AND MATERIALS: A study was performed on a group of 18 patients with cancer of the head and neck, lung, and pelvis who were treated with irregularly shaped fields. The BEV dosimetry of the fields shaped with cerrobend blocks and the MLC was measured with films at the depth of dose prescription in a solid water phantom. A "one-half-leaf" insertion convention was used to shape the MLC. In addition, an average of 15 sequential daily port films was taken per patient during the course of radiotherapy. The port films were aligned with the prescription film for each patient. Systematic error and random error of treatment setup for each patient were calculated. The effects of setup variation were incorporated by convolving the patient portal imaging data with the corresponding BEV film dosimetry. Two parameters were used to quantify the BEV dosimetry. First, the field penumbra width was calculated, which represented the average of the normal separations between 20 and 80% isodose lines along the prescription outline. Second, the ratio of areas covered by the 90 and 20% isodose lines, A90/20, was determined. The BEV dosimetry was then characterized with and without the effects of treatment setup variation. In addition, the difference in BEV dosimetry between the cerrobend block and the MLC was used to estimate the corresponding changes in tumor control probability (TCP). These changes were also compared to the changes in TCP for the treatment with or without the effects of random setup variation. RESULTS: With or without daily setup variation, the use of cerrobend block was more favorable than the MLC in terms of the field penumbra width and A90/20 for all treatment sites. In the absence of daily variation, the MLC field penumbra width was on average 1.3 mm larger than that of the cerrobend block, and 0.9 mm larger in the presence of daily setup variation. Similarly, the ratio A90/20 of the cerrobend block was on average 0.03 larger than that of MLC without daily setup variation, and 0.02 with daily setup variation. The difference in field penumbra width and A90/20 between the MLC and the cerrobend block was slightly reduced due to the effects of daily setup variation. For both the cerrobend block and the MLC, daily setup variation produced a significant increase in the field penumbra width, 2.3 mm for the cerrobend block and 1.9 mm for the MLC, and a decrease in the A90/20, 0.06 for the former and 0.05 for the latter. The change due to the daily setup variation was about a factor of 2 larger than the changes due to replacing the cerrobend block with the MLC. Using the TCP model, the change in TCP due to the daily setup variation was more than a factor of 3 larger than the change in TCP due to replacing the cerrobend block with the MLC. It was noted that the average changes in the penumbra, the A90/20 and the TCP calculated for the patient population did not adequately describe the changes for the individual patient. CONCLUSION: Our results do not show significant dosimetric differences between the MLC and the cerrobend block in conventional radiation treatment, whether or not daily setup variation was taken into consideration. The effects of daily setup variation alone produced a larger dosimetric change. The same results were obtained when the data were applied to calculate changes in TCP. For optimal radiation therapy, efforts should be concentrated on reducing daily setup variation. Our results also demonstrate the importance of frequent evaluation of MLC treatment using electronic portal imaging devices.

Equipment Design↗
PubMed1993

Postmortem changes in blood tranylcypromine concentration: competing redistribution and degradation effects.

Site and temporal changes in tranylcypromine (TCP) and lithium concentrations in blood were studied in a human poisoning case. Blood samples from peripheral vessels and six central vessels were obtained at 0, 6, 24, 48 and 72 h after starting the autopsy. Nine tissue samples were obtained on completion. TCP showed preferential concentration in liver (2.21 micrograms/g) and brainstem (2.46 micrograms/g). There was a moderate post mortem redistribution phenomenon with TCP concentrations lowest in peripheral blood (0.17 micrograms/ml) at 0 h and highest in central vessels at 24 h (0.52 micrograms/ml). At 72 h blood TCP concentrations fell below those at 0 time but the samples showed marked putrefactive changes. Control blood samples spiked with TCP and incubated for 48 h at 37 degrees C showed a 58% fall in drug concentration. By contrast with TCP, lithium, which has a small Vd (0.8 l/kg) and is chemically stable, did not show this pattern of change in blood concentration. The site and temporal differences in TCP concentration in blood can be explained by the competing effects of post mortem redistribution and drug degradation. Redistribution is an early post mortem phenomenon characterised by diffusion, along a concentration gradient, from drug reservoirs in solid organs into adjacent blood vessels. Drug degradation is a later phenomenon associated with putrefactive change.

Drug Overdose↗
PubMed1992

[125I]thienylphencyclidine, a novel ligand for the NMDA receptor.

We have monitored the binding of [125I]thienylphencyclidine ([125I]TCP), a novel high affinity radioiodinated ligand that specifically recognizes the NMDA (N-methyl-D-aspartate) receptor in rat brain membranes. [125I]TCP binds with an affinity of about 30 nM, and recognizes a similar number of binding sites to previously employed ligands for this receptor. [125I]TCP binding is characterized by slow association and dissociation rates, and the latter can be modified by the addition of Mg2+ or Zn2+, as previously described for [3H]dizocilpine ([3H]MK801). Other phencyclidine-like ligands displaced [125I]TCP binding with the order of potency dizocilpine greater than thienylphencyclidine greater than ITCP greater than phencyclidine greater than ketamine. The binding of [125I]TCP was also increased by NMDA and glycine-site agonists and inhibited by antagonists of these sites. Surprisingly, however, the polyamines spermidine and spermine did not increase [125I]TCP, even though the polyamine antagonist arcaine was an effective inhibitor of binding. These results show that [125I]TCP is a useful ligand for the NMDA receptor complex that binds to the receptor in a manner that is qualitatively distinct from previously described ligands.

Animals↗
PubMed2004

Evidence for heterodimers of 2,4,5-trichlorophenol on planar lipid layers. A FTIR-ATR investigation.

Trichlorophenols are weak acids of high hydrophobicity and are able to transport protons across the mitochondrial membrane. Thus the proton motive force is dissipated and the ATP production decreased. In situ Fourier Transform Infrared-Attenuated Total Reflection (FTIR-ATR) experiments with 2,4,5-trichlorophenol (TCP) adsorbed to model membranes resulted in good evidence for the formation of the TCP-heterodimer. Two surfaces were examined: a dipalmitoyl phosphatidic acid (DPPA) monolayer and a planar DPPA/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer. TCP was adsorbed from 1 to 3 mM solutions at pH 6.0 to the lipid layers leading to surface layers at the water/lipid interface. Difference spectra showed an effect on DPPA acyl chains even when it was covered with POPC. Time-resolved measurements revealed two distinct adsorption processes, which were assigned to TCP and its deprotonated anion (phenoxide), respectively. For DPPA/POPC bilayers, the adsorption of TCP was faster than that of its phenoxide, whereas adsorption of both species to DPPA monolayers proceeded with similar velocity. In both cases, phenoxide formation at the membrane was found to be delayed with respect to phenol adsorption. Phenoxide and phenol were retained after replacing the TCP solution with buffer. For the retained species, we estimated a phenol/phenoxide molar ratio of 1 at pH 6.0 (pKa=6.94 for TCP), demonstrating strong evidence for heterodimer formation.

Adsorption↗
PubMed2005

Bone formation and resorption of highly purified beta-tricalcium phosphate in the rat femoral condyle.

The aim of this study was to examine the chronological histology associated with highly purified beta-tricalcium phosphate (beta-TCP) implanted in the rat femoral condyle. Specimens were harvested on days 4, 7, 14, 28 and 56 after implantation, and were analyzed by tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry of the ED1 protein as a marker of the phagocyte system, and in situ hybridization with digoxigenin-labeled alpha1 chain of type I procollagen (COL1A1), osteopontin and osteocalcin. beta-TCP was resorbed in a chronological manner. Although new bone was not observed on day 4, fibroblast-like cells around beta-TCP were positive for COL1A1 and osteopontin mRNA. New bone formation presented after day 7. In the double-staining for OPN and ED1 on day 7, most cells around beta-TCP were positive for either osteopontin mRNA or ED1 protein. However, there were some doubly positive multinucleated cells, suggesting that they belonged to the mononuclear phagocyte system. After day 28, the implanted region was replaced with bone marrow. Multinucleated TRAP-positive and ED1-positive cells which adhered to beta-TCP at all stages seemed to be osteoclasts and they continuously resorbed beta-TCP. beta-TCP has a good biocompatibility since both bioresorption and bone formation started at an early stage after implantation.

Absorbable Implants↗
PubMed2005

The use of a bioresorbable nano-crystalline hydroxyapatite paste in acetabular bone impaction grafting.

Calcium phosphates such as TCP-HA granules are considered promising bone graft substitutes. In the future, they may completely replace allograft bone for impaction grafting procedures. Mechanically, acetabular reconstructions with TCP-HA granules show high stability, however this is partly caused by excessive cement penetration, which is unfavourable from a biological perspective. It has been hypothesised that mixtures of morselised cancellous bone grafts (MCB) and/or TCP-HA granules with a nano-crystalline hydroxyapatite paste (Ostim) may reduce cement penetration while maintaining adequate implant stability and biocompatibility of the graft mixture. To investigate this hypothesis, destructive lever-out tests and in vivo animal test were performed with various combinations of materials. Mechanically, the addition of 10% Ostim to mixtures of MCB and/or TCP-HA granules reduced cement penetration and resulted in a mechanical stability comparable to pure allograft (the current gold standard). Biologically, the application of Ostim with MCB or TCP-HA granules did not hamper the biocompatibility of the materials. Ostim was mostly osseous-integrated with MCB or TCP-HA granules after 8 weeks. Also, non-osseous-integrated Ostim remnants were observed. In tartrate resistant acid phosphatase stained sections, these few non-osseous integrated Ostim remnants were actively being resorbed by osteoclasts. In conclusion, Ostim HA-paste could be a valuable addition when TCP-HA ceramic granules are being used for acetabular bone impaction grafting procedures.

Absorbable Implants↗
PubMed2006

Repair of segmental bone defects in rabbit tibiae using a complex of beta-tricalcium phosphate, type I collagen, and fibroblast growth factor-2.

The objective of this study was to evaluate the effects of a complex of beta-tricalcium phosphate (beta-TCP) granules, collagen, and fibroblast growth factor-2 (FGF-2) on cortical bone repair in rabbits. Segmental bone defects of 5 mm in length were created in the middle of the tibial shaft. The defect was stabilized with a plate and screws, and was filled with 0.3 ml of a complex of beta-TCP granules and 5% collagen, with or without 200 microg of recombinant human fibroblast growth factor-2 (rhFGF-2). Bone regeneration and beta-TCP resorption were assessed by X-ray and micro-CT scanner. A three-point bending test was also performed. The results showed that the segmental bone defect was not only radiologically, but also mechanically healed with cortical bone 12 weeks after implantation of the complex with rhFGF-2. In contrast, after implantation of the complex without rhFGF-2, most of the defect was filled with beta-TCP and only a small amount of bone formation was found. These results suggest that resorption of beta-TCP is important for bone formation and may be promoted by FGF-2 in the beta-TCP implantation site. In addition, the complex of beta-TCP granules and collagen combined with rhFGF-2 provides a paste-like material that is easy to handle. This material may be of considerable use in the treatment of cortical bone defects.

Animals↗