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Modulation of Mg(2+)-dependent [3H]TCP binding by L-glutamate, glycine, and guanine nucleotides in rat cerebral cortex.

Biochemical and electrophysiological studies have demonstrated that phencyclidine (PCP) recognition site exists in the ion channel of the N-methyl-D-aspartate (NMDA) receptor ion channel complex. Using an extensively washed rat cortical membrane preparation, the effects of Mg2+ and guanylylimidodiphosphate (GppNHp) were examined on the binding of [3H]-N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP). Low concentrations of Mg2+ (EC50 = 11 microM) stimulated [3H]TCP binding under the basal condition and high concentrations of Mg2+ (IC50 = 1 mM) inhibited it. In the presence of 10 microM L-glutamate and 10 microM glycine, their EC50 values for Mg2+ enhancement of [3H]TCP binding were markedly reduced (to 1.9 microM or 8.4 microM), respectively. By contrast, the IC50 values for Mg2+ inhibition of [3H]TCP binding were reduced in the presence of L-glutamate, but not glycine. Furthermore, a stimulatory effect of Mg2+ on [3H]TCP binding was additional to the [3H]TCP binding stimulated by a maximally effective concentration of L-glutamate (10 microM) or glycine (10 microM). In the kinetic study, 300 microM Mg2+ produced an increase in the rates of both association and dissociation of [3H]TCP. Similar results were obtained with L-glutamate (10 microM) and glycine (10 microM); 10 mM Mg2+ also caused an acceleration of the association rate but strongly decreased [3H]TCP binding at equilibrium. Compared with [3H]TCP binding under the basal condition, K+ (10 mM) alone decreased the maximal binding without producing any change in the association rate; 10 mM K+ also significantly decreased Mg(2+)-stimulated [3H]TCP binding but caused no change in the acceleration of the association rate caused by Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Isolation and characterization of a cDNA clone corresponding to the mouse t-complex gene Tcp-1x.

The mouse t complex on chromosome 17 is known to harbour many genes which have an important role in spermatogenesis. One of these, Tcp-1 has been cloned and shown to code for a protein probably essential for acrosome formation. During the isolation of a cDNA for Tcp-1 two other homologous sequences were recognized and described as Tcp-1x and Tcp-1y. In this paper we describe the isolation of a cDNA which has been shown by in situ hybridization to correspond to the Tcp-1x gene. Sequence analysis has confirmed that a 140 bp region of homology between Tcp-1 and Tcp-1x lies in the 3' portion of both genes. Northern blotting has revealed that the Tcp-1x gene is expressed abundantly in liver where two transcripts are detectable and hybrid selection shows that the gene codes for a 37 kDa protein. A search of the DNA database has failed to find any significant homology between Tcp-1x and any other sequences apart from Tcp-1.

Amino Acid Sequence↗

Enhanced osteoinduction by intramuscular grafting of BMP-beta-TCP compound pellets into murine models.

The osteoinductive effects of bone morphogenetic protein (BMP, derived from murine osteosarcoma) were studied with regard to its use combined with beta-tricalcium phosphate (beta-TCP). BMP and beta-TCP were molded into pellets by the "pressure method", originated by us and transplanted to ddY mice. Control mice received interdorsal muscular implantations of either the BMP or beta-TCP pellets. The animals were sacrificed 1, 2 and 3 weeks after grafting, for radiological, histochemical, and ultrastructural observations. The BMP-beta-TCP compound pellets induced faster cartilage and bone formation, whereas these activities were slower when pellets made solely of BMP were used. The beta-TCP pellets demonstrated no osteoinductive properties. Observations revealed two types of beta-TCP resorbing multinuclear giant cells. One was osteoclastic, expressing calcitonin receptors, having numerous mitochondria and ruffled border-like structures; the other was not osteoclastic in nature. In animals grafted with the compound pellets, a great number of osteoclastic cells gathered on the pellets, much earlier than those grafted with the pellets made of BMP alone. Then, osteoblastic bone formation over the cement lines followed an osteoclastic resorption of both beta-TCP and newly formed bone. In contrast, BMP induced few osteoclastic cells, resulting in slower bone coupling. Furthermore, the faster bone formation induced by the compound pellets seemed to be associated with the presence of beta-TCP. Porous by nature, beta-TCP would entrap BMP within its micropores, and thus, the intrinsically diffusible BMP is retained and its action consequently prolonged. In addition, the compound pellet offered increased surface contact between BMP and mesenchymal cells. Therefore, BMP-beta-TCP compound pellets induce cartilage and bone formation more rapidly than does BMP alone.

Animals↗

Beneficial effects of TCP on soman intoxication in guinea pigs: seizures, brain damage and learning behaviour.

Poisoning with the potent nerve agent soman produces a cascade of central nervous system (CNS) effects characterized by severe convulsions and eventually death. In animals that survive a soman intoxication, lesions in the amygdala, piriform cortex, hippocampus and thalamus can be observed. In order to examine the mechanisms involved in the effects of soman and to evaluate possible curative interventions, a series of behavioural, electrophysiological and neuropathological experiments were carried out in the guinea pig using the NMDA antagonist N-[1-(2-thienyl)cyclohexyl] piperidine (TCP) in conjunction with atropine and pyridostigmine. The NMDA antagonist TCP appeared to be very effective in the treatment of casualties who suffered from soman-induced seizures for 30 min: (i)Seizures were arrested within minutes after the TCP injection, confirmed by quantitative electroencephalogram (EEG), after fast Fourier analysis. Three hours after TCP the quantitative EEGs were completely normal in all frequency bands and remained normal during the entire 3-week intoxication period. The power shift to the lower (delta) frequency bands, indicative for neuropathology and found in control animals intoxicated only by soman, was not observed in the soman-TCP group. (ii)The gross neuropathology found in soman control animals within 48 h after soman was prevented in soman-TCP animals and was still absent in 3-week survivors. Instead, ultrastructural changes were observed, indicative of defense mechanisms of the cell against toxic circumstances. (iii)Twenty-four hours after soman, soman-TCP animals were able to perform in the shuttle box and Morris water maze. The beneficial effects of TCP on the performance in these tests during the 3-week intoxication period were very impressive, notwithstanding (minor) deficits in memory and learning. (iv)The increase in excitability after TCP was confirmed by an increase in the acoustic startle response. Taken together, these results confirmed the involvement of NMDA receptors in the maintenance of soman-induced seizures and the development of brain damage. They underline the current hypothesis that cholinergic mechanisms are responsible for eliciting seizure activity after soman and that, most likely, the subsequent recruitment of other excitatory neurotransmitters and loss of inhibitory control are responsible for the maintenance of seizures and the development of subsequent brain damage.

Animals↗

[Intra-individual comparison of alpha- and beta-TCP ceramics in an animal experiment].

In the quest for bioinert adaptable alloplastic materials, TCP ceramics have gained a new application in craniofacial bone substitutes. Therefore, a histomorphological, intraindividual, comparative study was conducted on seven adult Goettingen miniature pigs (GMP) to analyze the difference of the degradation and remodelling processes of alpha-TCP and beta-TCP in critical size defects of the proximal tibiae. In addition, primary insertion of dental implants followed to study osseous integration. The critical size defects, which were created in the proximal tibiae in GMPs, were filled on the left side with beta-TCP and on the right side with alpha-TCP. Two GMPs were used as control group. After 4-68 weeks of investigation, the GMPs were sacrificed by narcosis. The histological investigation showed that these ceramics have an osteoconductive effect. It was noted that ossification proceeds centripetally. It could be demonstrated that the degradation of the materials follows a hydrolytical process and that the intratrabecular integrated ceramic remnants follow a dynamic remodelling process. Within 68 weeks after implantation, 90% of the TCP granulae were degraded. Macrophages were found in the marrow space, containing microparticles of TCP, especially after alpha-TCP implantation. In conclusion, defined degradation of these ceramics allows early functional bone regeneration with an additional undisturbed biofunctional unisotrop orientation of new trabeculae. Furthermore, dental implants should be inserted 5-6 months after TCP implantation.

Animals↗

Nucleotide sequence of mouse Tcp-1a cDNA.

We have isolated complete cDNA clones encoding the mouse t-complex polypeptides 1A and 1B (TCP-1A and TCP-1B) from t-haplotype and wild-type (wt) mice, respectively. The complete nucleotide (nt) sequence of the Tcp-1a cDNA was determined. The Tcp-1a cDNA has an open reading frame (ORF) encoding a 60-kDa protein of 556 amino acids (aa). A comparison of nt sequences between the Tcp-1a and Tcp-1b cDNAs revealed that the 1786-bp regions upstream from their polyadenylation signals differed by 17 substitutions and that Tcp-1a had different polyadenylation sites from Tcp-1b. In these ORFs, 15 bp were substituted between the two alleles, occurring in 14 codons and resulting in eleven single-aa substitutions. Among these 15 substitutions, twelve were nonsynonymous (aa change) and three were synonymous (no aa change). The aa substitution in TCP-1 has occurred at least 20 times faster between t-haplotype and wt than between mouse and human or mouse and Drosophila.

Amino Acid Sequence↗

DNA binding and dimerization specificity and potential targets for the TCP protein family.

The TCP domain is a plant-specific DNA binding domain found in proteins from a diverse array of species, including the cycloidea (cyc) and teosinte branched1 (tb1) gene products and the PCF1 and PCF2 proteins. To understand the role in transcriptional regulation of proteins with this domain, we have analysed the DNA binding and dimerization specificity of the TCP protein family using rice PCF proteins, and further evaluated potential targets for the TCP protein. The seven PCF members including five newly isolated proteins, were able to be grouped into two classes, I and II, based on sequence similarity in the TCP domain. Random binding site selection experiments and electrophoretic mobility shift assays (EMSAs) revealed the consensus DNA binding sequences of these two classes to be distinct but overlapping; GGNCCCAC for class I and GTGGNCCC for class II. The TB1 protein from maize, which belongs to class II, had the same specificity as the rice class II proteins, suggesting the conservation of binding specificity between TCP domains from different species. The yeast 2-hybrid assay and EMSA revealed that these proteins tend to form a homodimer or a heterodimer between members of the same class. We searched predicted 5' flanking sequences of Arabidopsis genes for the consensus binding sequences and found that the consensus sites are distributed in the genome at a considerably lower frequency. We further analysed eight promoters containing the class I consensus TCP sites. The transcriptional activities of six promoters were decreased by a mutation of the TCP binding site, which is consistent with the observation that the class I TCP site can confer transactivation function on a heterologous promoter. These results suggest that the two classes of TCP protein are distinct in DNA binding specificity and transcriptional regulation.

Amino Acid Sequence↗

The pharmacokinetics of [3H]1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) in Sprague-Dawley rats.

Using adult male Sprague-Dawley rats, we examined the blood protein binding and pharmacokinetics of the potent phencyclidine (PCP) receptor ligand 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP). The average percentage of unbound [3H]TCP in rat serum was 42 +/- 6% and the [3H]TCP blood to plasma ratio was 0.98 +/- 0.03 (mean +/- SD, n = 5 in both studies). For the pharmacokinetic studies, [3H]TCP and 1 mg/kg unlabeled TCP were administered as an iv bolus dose. The average [3H]TCP elimination half-life was 2.1 hr. In contrast, total radioactivity in the plasma had a much longer half-life, suggesting much slower metabolite elimination. The average distribution volumes were 27 +/- 17, 15.6 +/- 6.2, and 5.6 +/- 3.0 liters/kg for V beta, Vss, and Vc, respectively. Total body and renal clearance values were 132 +/- 45 and 1.1 +/- 0.4 ml/min/kg, respectively. When TCP pharmacokinetic parameters were compared to PCP pharmacokinetic data in rats from a previous study, a strikingly similar pharmacokinetic profile was found. These data indicated that TCP and PCP are equivalent, from a pharmacokinetic point of view, and that the higher pharmacological potency of TCP over PCP is probably due to receptor-mediated differences.

Animals↗

Anticonvulsant and antilethal effects of the phencyclidine derivative TCP in soman poisoning.

The protection afforded by TCP (thienylcylohexylpiperidine), a non-competitive blocker of N-methyl-D-aspartate (NMDA) receptors, against the seizures and lethality produced by 2 x LD50 of soman (62 micrograms/kg, sc), an irreversible inhibitor of cholinesterase, was studied in guinea-pigs. In the presence of additional anticholinergic medication (pyridostigmine: 0.2 mg/kg, sc, 30min prior to soman; atropine sulphate: 5mg/kg, im, 1 min post-soman), TCP pretreatment (2.5mg/kg, im, 30 or 15 min prior to soman) did not generally prevent the appearance of soman-induced status epilepticus but did arrest it after 30-40 min in 80% (TCP-30min) or 100% (TCP-15min) of the convulsing subjects. Moreover, in all subjects treated curatively, TCP was able to interrupt ongoing status epilepticus in approximately 20, 10 or 8 min when it was administered 5, 30 or 60min respectively after the onset of epileptiform tracings on EEG. All of these curatively administered animals survived and recovered remarkably well. On every criteria examined (latency-to-seizure arrest, 24hr-survival rate, clinical recovery), injection of 2.5mg/kg TCP after 90min of seizures appeared slightly less efficient compared to earlier curative administration. Therefore, our study (a) establishes that the previously reported capacity of MK-801 (dibenzocyclohepneimine) to counteract soman toxicity is not unique and could be extended to other non-competitive inhibitors of NMDA receptors; (b) shows that TCP could easily prevent and, above all, interrupt soman-induced seizures; furthermore, TCP appears the first compound ever tested on soman poisoning that still displays satisfactory anticonvulsant activity after such a long duration of initial status epilepticus (90min); therefore, TCP might be of special value for the delayed therapy for soman poisoning; (c) confirms that NMDA receptors are involved in the maintenance of seizures and play an important role in other processes implicated in the overall toxicity (including the lethal respiratory effects) of soman poisoning.

Animals↗

Temporal and spatial patterns of osteoblast activation following implantation of beta-TCP particles into bone.

Temporal and spatial patterns of osteoblast activation around beta-TCP particles implanted into bone were analyzed by in situ hybridization with digoxygenin-labeled procollagen alpha 1(I) RNA probes. beta-TCP particles (150-300 microns in diameter) were implanted into rat tibiae, and specimens were collected 3, 5, 7, 14, and 28 days after operation. Activated osteoblasts displayed intense procollagen alpha 1(I) RNA specific labeling. At day 3, osteoblasts lining pre-existing trabeculae in places showed a specific signal. Additionally, scattered activated cells compatible with preosteoblasts also were observed in the vicinity of the trabeculae among red blood cells that filled the space between beta-TCP particles. Osteoblast activation on the surface of beta-TCP rarely was observed. At days 5 and 7, osteoblast activation and bone formation advanced centripetally. At the forefront of bone formation positive cells were scattered in the blood cell clots, and some of the positive cells colonized forming new bone matrix. Formation of new bone did not always begin at the surface of beta-TCP. At day 14, most of the beta-TCP particles were tightly associated with newly formed bone, and the number of positive osteoblasts was reduced. At day 28, absorption of the newly formed bone and the beta-TCP by multinuclear cells was sporadically demonstrated. Such cells often were accompanied by active osteoblasts, suggesting early bone remodeling. In conclusion, in situ hybridization with procollagen alpha 1(I) was employed to demonstrate precisely the mode of recruitment of bone cell precursors. beta-TCP does not positively guide collagen I expressing bone cells along its surface. It has no apparent effects on bone regeneration.

Animals↗

Differential modulation of [3H]TCP binding to the NMDA receptor by L-glutamate and glycine.

At equilibrium (4 h incubation), [3H]TCP (N-(1-[2-thienyl]-cyclohexyl)-3,4-[3H]piperidine) binding to well-washed rat forebrain membranes was enhanced in a concentration-dependent and 2-APV (2-amino-5-phosphonovaleric acid)-sensitive fashion by L-glutamate (EC50 = 0.2 microM; maximal effect +280%). L-glutamate (10 microM) increased the affinity of [3H]TCP from 78 to 28 nM, but was without effect on the maximal binding capacity. The enhancing effect of L-glutamate on [3H]TCP binding was potentiated by glycine in a concentration-dependent manner (EC50 = 50 nM, maximal effect +30% in the presence of 10 microM L-glutamate; EC50 = 2 microM, maximal effect +29% in the presence of 0.1 microM L-glutamate). This effect was strychnine-insensitive. Glycine failed to enhance [3H]TCP binding in the presence of 10 microM 2-APV. The glycine effect was due to an increase in affinity (Kd = 21 nM in the presence of 10 microM glycine and 10 microM L-glutamate); glycine did not affect the maximal binding capacity. The glycine enhancement of L-glutamate-stimulated [3H]TCP binding was not antagonised by 1 microM strychnine and was mimicked by L-serine and L-alanine but not by GABA, taurine or beta-alanine. Kinetic analysis of the glycine and L-glutamate enhancement of [3H]TCP binding indicated that the L-glutamate effect was related to a decrease in the [3H]TCP dissociation rate while the glycine effect was due to an increase in the rate of [3H]TCP association in the presence of L-glutamate.

Animals↗

Structure and expression of the gene encoding mouse t-complex polypeptide (Tcp-1).

The nucleotide (nt) sequence of the structural gene (Tcp-1) encoding mouse t-complex polypeptide 1 (TCP-1) has been determined. The nt sequence extending to 10,043 bp shows that the Tcp-1 gene is divided into 12 exons, 11 introns and 5'- and 3'-flanking regions. The Tcp-1 gene has a tight cluster of major transcription start points (tsp). Two GC boxes, one CCAAT box and some other possible regulatory elements are located in the region upstream from the tsp, but no TATA box was found. Extending from the 5'-flanking region to the first intron, a CpG dinucleotide-rich cluster is located. In addition, Tcp-1 gene transcripts in mouse organs, embryos and cultured cells were analyzed by Northern blotting. The Tcp-1 mRNA is enriched not only in testes, but also in early post-implantation embryos and some cultured cell lines, as compared with mouse organs other than the testis. The amount of Tcp-1 mRNA in embryos decreases during development. These results suggest that the expression of the Tcp-1 gene may be regulated spatially and temporally in embryonic and adult mice by transcriptional control or by mRNA stability.

Amino Acid Sequence↗

2,4,5-T and 2,4,5-TCP induce oxidative damage in human erythrocytes: the role of glutathione.

The molecular basis of the toxic properties of phenoxy herbicides in humans and animals has been insufficiently studied. In this study, damage parameters [levels of reduced glutathione (GSH) and total glutathione; activity of glutathione reductase (GR); activities of catalase (CAT) and superoxide dismutase (SOD); levels of adenine nucleotides and adenine energy charge (AEC)] were measured in human erythrocytes exposed in vitro to 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and its metabolite 2,4,5-trichlorophenol (2,4,5-TCP). Both 2,4,5-T and 2,4,5-TCP decreased the level of reduced glutathione (GSH) in erythrocytes in comparison to the control, but did not significantly change the total glutathione (2GSH + GSSG). This suggests that GSH concentration decreases concomitantly with an increase in oxidized glutathione (GSSG). 2,4,5-TCP at 100 ppm significantly decreased catalase and SOD activities. 2,4,5-T and 2,4,5-TCP did not significantly change the activity of glutathione reductase. 2,4,5-TCP decreased the level of ATP and increased the content of ADP and AMP, indicating a fall in AEC. 2,4,5-T and 2,4,5-TCP significantly changed the erythrocyte morphology. All these data are evidence of oxidative stress in erythrocytes incubated with 2,4,5-T and 2,4,5-TCP; the stress appears to be more intense in the case of 2,4,5-TCP.

2,4,5-Trichlorophenoxyacetic Acid↗

The delta-TCP concept: a clinically useful measure of tumor control probability.

PURPOSE: The aim of this article is to provide a quantitative tool to evaluate the influence of the different dose regions in a non-uniformly irradiated tumour upon the probability of controlling that tumor. METHODS AND MATERIALS: First, a method to generate a distribution of the probability of controlling the cells in a voxel (VCP) is explored and found not to be useful. Second, we introduce the concept of delta-TCP, which represents the gain or loss in the overall TCP as a result of each particular bin in a DVH not receiving the prescribed dose (the same concept is applicable to dose cubes or to a fraction of the bin). The delta-TCP method presented here is based on the Poisson TCP model, but any other model could also be used. Third, using this tool, with parameters appropriate to Stage C prostate tumors, the consequences of "cold" and "hot" dose regions have been explored. RESULTS: We show that TCP is affected by the minimum dose, even if it is delivered to a very small volume (20% dose deficit to 5% of the volume makes the TCP decrease by 18%), and that a hot region may be "wasted" unless the boost is to the bulk of the volume. An example of the application of the delta-TCP concept to a prostate radiotherapy plan is also given. CONCLUSION: The delta-TCP distribution adds more objective information to the original DVH by enabling the clinician or planner to directly evaluate the effects of a non-uniform dose distribution on local control.

Algorithms↗

Sintering and characterization of HA and TCP bioceramics with control of their strength and phase purity.

HA and beta-TCP-based ceramics were prepared using commercial powders. Powder characteristics were defined and the processing parameters studied, aimed at the production of samples with improved microstructural and mechanical properties. The behaviour of HA powder subjected to various thermal treatments was investigated in order to control the formation of secondary phases (alpha- and beta-TCP) during sintering. The optimal thermal treatment required to prepare pure beta-TCP powder from the precursors (HA and DCP) was determined and the sintering method required to prepare fully dense beta-TCP completely free from alpha-form, was identified. Translucent hot-pressed beta-TCP ceramics with potential applications in aesthetic restorative prostheses were prepared and characterized. The interval of existence of alpha-TCP and alpha-TCP as secondary products was also defined. Crystallographic analysis was carried out on the imperfectly known low-temperature alpha-TCP phase, and a proper monoclinic unit cell determined.

Journal Article↗

Secretion of a soluble colonization factor by the TCP type 4 pilus biogenesis pathway in Vibrio cholerae.

Colonization of the human small intestine by Vibrio cholerae requires the type 4 toxin co-regulated pilus (TCP). Genes encoding the structure and biogenesis functions of TCP are organized within an operon located on the Vibrio Pathogenicity Island (VPI). In an effort to elucidate the functions of proteins involved in TCP biogenesis, in frame deletions of all of the genes within the tcp operon coding for putative pilus biogenesis proteins have been constructed and the resulting mutants characterized with respect to the assembly and function of TCP. As a result of this analysis, we have identified the product of one of these genes, tcpF, as a novel secreted colonization factor. Chromosomal deletion of tcpF yields a mutant that retains in vitro phenotypes associated with the assembly of functional TCP yet is severely attenuated for colonization of the infant mouse intestine. Furthermore, we have determined that the mechanism by which TcpF is translocated across the bacterial outer membrane requires the TCP biogenesis machinery and is independent of the type II extracellular protein secretion (EPS) system. These results suggest a dual role for the TCP biogenesis apparatus in V. cholerae pathogenesis and a novel mechanism of intestinal colonization mediated by a soluble factor.

Animals↗

Viability of the EUD and TCP concepts as reliable dose indicators.

The concept of equivalent uniform dose (EUD) was introduced to provide a method of reporting radiotherapy dose distributions which takes account of the nonlinearity of tissue dose-response, whilst not attempting to make predictions of absolute outcome. The purpose of this investigation was to determine the level of sensitivity of EUD to model parameters for significant variations in dose distribution and consequently the reliability of the factor as a dose-indicator, and to compare EUD with the more familiar index, tumour control probability (TCP). EUD and TCP, derived from the linear-quadratic formalism, were investigated for a test tissue being irradiated non-uniformly. Variations in the parameters of the model (tissue cell characteristics, dose heterogeneity, fractionation parameters) indicated the sensitivity of EUD and TCP to them. For time independent factors--cell density, cell radiosensitivity, radiosensitivity heterogeneity (population averaged) and ratio alpha/beta--EUD was found to vary insignificantly in comparison with TCP, though this is a function of the actual form of the dose distribution under consideration. For fractionated treatments where the mean dose per fraction is varying (due to dosimetric/positioning errors for example), both EUD and TCP showed little variation with the degree of dose non-uniformity. For other time dependent factors, fractionation rate and cell repopulation times, TCP again showed significant variation relative to EUD. The relative insensitivity of EUD implies that this index will be useful for dose evaluation when parameters are not known with accuracy, for the intercomparison of dose control studies and as a radiobiologically based optimization objective. However, given confidence in model parameters, the sensitivity of TCP would make it a more reliable tool for indicating potentially successful and unsuccessful irradiation strategies. It is suggested that both parameters be used in conjunction, with EUD and TCP results viewed with an appreciation of the characteristics of each model.

Dose Fractionation, Radiation↗

Apatite formation in composites of alpha-TCP and degradable polyesters.

The objective of this study was to investigate the conversion of alpha-Ca3(PO4)2 (alpha-TCP) in composite bone cements based on a water-degradable polyester matrix as a function of the polymer formulation and the alpha-TCP filler content. Cross-linkable dimethacrylates of epsilon-caprolactone/ D,L-lactide co-polymer or of epsilon-caprolactone/glycolide co-polymer were mixed with hydroxyethylmethacrylate, a photo-initiator and alpha-TCP to obtain composites with a filler content of 80 or 40 wt% alpha-TCP. The disk shaped composite samples were set by visible light irradiation and immersed in HEPES at 37 degrees C. At selected times the samples were removed from the solution and analysed with X-ray diffractometry and infrared spectroscopy. Conversion of alpha-TCP into calcium-deficient hydroxyapatite (CDHAp) was observed for all composites, but the reaction was not completed after 8 weeks immersion. The conversion rate of alpha-TCP and the crystallinity of the formed apatite apparently were not affected by the type of polyester used, but significantly depended on the alpha-TCP content of the composites. An increase of the amount of alpha-TCP in the composite resulted in a slower formation of CDHAp with a higher crystallinity.

Apatites↗