Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TCP”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed1994

Comparison of the urinary metabolite profiles of hexachlorobenzene and pentachlorobenzene in the rat.

The urinary metabolite profile of hexachlorobenzene (HCB) and pentachlorobenzene (PCBz) in the rat is compared after dietary exposure for 13 weeks. Both HCB and PCBz are oxidized to pentachlorophenol (PCP) and tetrachlorohydroquinone (TCHQ), which were the only two mutual metabolites formed. Additional urinary metabolites of HCB are N-acetyl-S(pentachlorophenyl)cysteine (PCTP-NAC), which appeared to be quantitatively the most important product, and mercaptotetrachlorothioanisole (MTCTA), which was excreted as a glucuronide. PCBz is more extensively metabolized to the major metabolites 2,3,4,5-tetrachlorophenol (TCP), mercaptotetrachlorophenol (MTCP) and the glucuronide of pentachlorothiophenol (PCTP), and the minor metabolites methylthiotetrachlorophenol (MeTTCP), hydroxytetrachlorophenyl sulphoxide (HTCPS), and bis(methylthio)-trichlorophenol (bis-MeTTriCP). The biotransformation of HCB and PCBz was modulated by selective inhibition of cytochrome P450IIIA in rats which received combined treatment of HCB or PCBz with triacetyloleandomycin (TAO). Rats receiving this diet had a strongly diminished excretion of both PCP and TCHQ, as compared to rats fed HCB or PCBz alone, indicating the involvement of P450IIIA in the oxidation of both compounds. However, the excretion of 2,3,4,5-TCP was not diminished by co-treatment of rats with PCBz and TAO, indicating that: (i) the oxidation of PCBz to PCP and 2,3,4,5-TCP does not proceed via a common intermediate; and (ii) oxidation of PCBz to 2,3,4,5-TCP is not mediated by P450IIIA. Co-treatment of rats with PCBz and TAO had a differential effect on the excretion of sulphur-containing metabolites, resulting in a decrease in the excretion of PCTP glucuronide, whereas no change was observed in the excretion of MTCP, as compared to rats receiving PCBz alone. The observed differences in HCB and PCBz metabolites clearly deserve further in vitro studies to elucidate their origin.

Animals↗
PubMed1983

Effects of central monoamine compounds on tranylcypromine-induced barbital-withdrawal convulsions.

Challenge with tranylcypromine (Tcp) during barbital (B) withdrawal induces dose-related clonic-tonic convulsion (C-TC), which is also related to the severity of withdrawal signs and their changes with the passage of time. The effects of neuropharmacological agents on the Tcp-induced convulsions were observed. dl-Propranolol, phentolamine, phenoxybenzamine and methysergide had been administered intraperitoneally 20 approximately 30 minutes before Tcp challenge. B-withdrawn rats had been pretreated with alpha-methyl-p-tyrosine, 5-hydroxytryptophan, p-chlorophenylalanine or reserpine, or with the combination of iproniazid and reserpine (5 hrs after iproniazid administration) before Tcp challenge. alpha-MT and dl-propranolol inhibited B withdrawal convulsion markedly, though high doses of dl-propranolol rather tended to show a less effect on the convulsion. alpha-Adrenoceptor blockers scarcely inhibited the convulsion. Methysergide or 5-HTP failed to inhibit, but PCPA intensified the convulsion. Reserpine, when administered alone, aggravated the convulsion, but when administered after iproniazid, inhibited it significantly. These findings suggested that the balance between the activities of noradrenergic and serotonergic neurons might be of importance in the manifestation of B withdrawal convulsions, the former probably being excitatory and the latter, inhibitory.

Animals↗
PubMed1991

Quantitative characterization of multiple binding sites for phencyclidine and N-allylnormetazocine in membranes from rat and guinea pig brain.

Quantitative ligand binding studies have been used to characterize binding sites for N-allylnormetazocine ((+)SKF10,047) (SKF), 1-(1-phenylcyclohexyl) piperidine (PCP), N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) and haloperidol in membranes from the brain of rat and guinea pig under conditions which permitted simultaneous analysis of the binding of both PCP and SKF. Using four labelled ligands (SKF, TCP, PCP and haloperidol), each displaced by the corresponding four unlabelled ligands, four classes of binding sites were observed in membranes from the brain of the rat, corresponding to sigma (sigma), two classes of PCP sites (PCP1, PCP2) and dopamine (D2) sites. The sigma site was suppressed by 50 nM haloperidol, while the PCP1 and PCP2 sites were not. These results were confirmed by studies employing a self- and cross-displacement design and dose-response surfaces for SKF and TCP, with and without blockade by haloperidol of the sigma site. Using mathematical modelling, employing the program LIGAND, it was possible to reject simpler models involving a common "PCP/sigma" site or a model involving only two classes of sites (sigma and PCP). Similar methods were used to identify two classes of sigma binding sites and two classes of PCP binding sites, in membranes prepared from the brain of the guinea pig. The relative potencies of 18 ligands for displacement of (+)[3H]SKF10,047 and [3H]TCP were compared: there were significant qualitative and quantitative differences in the "sigma" binding sites in the brain of rat and guinea pig, while the PCP binding sites were very similar in the two species.

Animals↗
PubMed1993

Multiple structural determinants of voltage-dependent magnesium block in recombinant NMDA receptors.

The voltage-dependent block of NMDA channels by Mg2+ is an important functional element of NMDA receptors, since relief of block by depolarization plays a key role in some forms of ischemic neurodegeneration and synaptic plasticity. To identify the relevant structural domains responsible for block by Mg2+ and TCP, we used site-directed mutagenesis to change individual amino acids of the rat NR1A subunit in a transmembrane region (599-DALTLSSAMWFSWGVLLNSGIGE-621, mutated residues underlined) previously shown to donate residues that influence ionic selectivity. Ten mutant NR1A subunits were co-expressed in Xenopus oocytes with either the epsilon 1 or NR2A subunits, and receptor properties were analyzed under two-electrode voltage clamp. The mutation N616R virtually abolished voltage-dependent Mg2+ block, reduced Zn2+ block 5-fold and greatly reduced Ba2+ permeability in confirmation of previous reports. This mutation also reduced the potency of TCP as a use-dependent blocker by 200-fold. The remaining low-affinity TCP block did not appear to be use-dependent, suggesting two blocking sites for TCP. None of the other mutations differed significantly from NR1A itself except S617N, which displayed a 6-fold reduction in Mg2+ block. A well-barrier model of permeation through the NMDA receptor channel is presented that quantitatively reproduces voltage-dependent Mg2+ block. This model demonstrates that only minimum changes energy profiles experienced by permeating ions, equivalent to the energy of a single hydrogen or ionic bond, are required to abolish Mg2+ block. These findings indicate that only small structural changes are needed to convert a Mg(2+)-insensitive ion channel to a channel with pronounced voltage-dependent Mg2+ block.

Amino Acid Sequence↗
PubMed1989

Calcium phosphate cements: study of the beta-tricalcium phosphate--monocalcium phosphate system.

The possibility of making cements based on beta-tricalcium phosphate (beta-TCP), a promising bone graft material, was investigated. Upon admixture with water, beta-TCP/monocalcium phosphate monohydrate (MCPM) mixtures were found to set and harden like conventional hydraulic cements. Beta-TCP powders with larger particle size, obtained by sintering at higher temperatures, increased the ultimate strength of the cement. Results show that setting occurs after dissolution of MCPM, as a result of the precipitation of dicalcium phosphate dihydrate (DCPD) in the paste. The ultimate tensile strength of the hardened cement is proportional to the amount of DCPD formed. Upon ageing above 40 degrees C, DCPD transforms progressively into anhydrous dicalcium phosphate (DCP), thereby decreasing the strength. Ageing of the pastes in 100% r.h. results in a decay of the mechanical properties. This can be ascribed to an intergranular dissolution of the beta-TCP aggregates as a result of the pH lowering brought about by the MCPM to DCPD conversion.

Biocompatible Materials↗
PubMed1995

Development of calcium phosphate based functional gradient bioceramics.

A functional gradient bioceramic that can function gradually with respect to body tissue was studied by changing the composition of calcium phosphate gradually from the surface to the inside. Diamond powder was spread on the surface of compact hydroxyapatite (HA) powder and fired at 1280 degrees C under reduced pressure, followed by firing under atmospheric conditions. The sintered body thus prepared was dense and alpha-tricalcium phosphate (alpha-TCP: alpha-Ca3(PO4)2) was found on its surface. The content of alpha-TCP gradually decreased with increasing depth from the surface. In contrast, the content of HA increased with increasing depth from the surface. The gradient ratio of alpha-TCP and HA depends on the firing time for each condition, i.e. reduced or atmospheric pressure. The alpha-TCP formation was ascribed to the decomposition of HA due to the spontaneous combustion of diamond powder.

Biocompatible Materials↗
PubMed1989

Clinical radiobiology of malignant melanoma.

Tumor-control probability (TCP) was analyzed in a series of 121 patients having 239 histologically proven recurrent or metastatic malignant melanomas. These were treated with fractionated radiotherapy with various doses per fraction, total doses, and overall times. Cutaneous lesions (127, 53%) were treated with electron beams, and more deeply seated tumors (112, 47%) with 60Co or 4-8 MV X-rays. The fraction size was highly variable, and this permitted determination of the alpha/beta ratio in the multifraction linear-quadratic model, which was estimated at 0.57 Gy with 95% confidence limits [-1.07, 2.5] Gy. Treatment time had no demonstrable influence on TCP. Thus this tumor exhibits the fractionation sensitivity characteristic of a late-responding normal tissue, suggesting that an adequate fractionation schedule for malignant melanomas would be characterized by larger-than-conventional doses per fraction, possibly about 6 Gy per fraction. This is consistent with the conclusions of other authors. Tumor size, evaluated as mean tumor diameter, S, had a major impact on TCP: the number of target cells increased as a power function of S with exponent 0.72 (95% confidence limits [0.49, 0.94]. In fact, a considerable amount of the heterogeneity in the dose-response data could be removed by accounting for size. Thus, the weak or absent dose response became highly significant. When a patient had multiple lesions, the responses of these to radiotherapy tended to be similar, thus implying that results were significantly influenced by a "hidden parameter" (such as inherent radiosensitivity or immunological status). A test of the predictive value of the TCP-model was performed in a different series of 183 cutaneous and lymph node malignant melanomas. The observed dose-response relationship in this data set was in good agreement with the model prediction. A chi-square test for goodness-of-fit showed that the variation between predicted and observed results could be explained by the binomial variation on quantal response data.

Cobalt Radioisotopes↗
PubMed1994

A comparison of proton and megavoltage X-ray treatment planning for prostate cancer.

Conformal photon and proton therapy plans for prostate cancer have been compared in an attempt to quantify the potential advantages of using protons. Two X-ray plans (3-field, 6-field) and a 2-field proton plan were made and compared for each of 20 T3 prostate patients with the aid of the 3D planning system VOXELPLAN. Dose distributions were analysed in terms of dose-volume histograms (DVH). Tumour control probability (TCP) and normal tissue complication probability (NTCP) were computed using our own and the Lyman-Kutcher-Burman models, respectively. The study shows that on average the proton technique results in the best dose distribution, giving the lowest rectal complication probability, and also that the 3-field X-ray technique is more effective than the 6-field X-ray technique in sparing the rectum. At 5% rectal NTCP, the predicted proton average TCP for the 20 patients is 2% (in absolute terms) greater than that obtained using 3-field X-ray therapy. For 7 of the patients the gain in TCP is more than 3%. For the same rectal NTCP as the 3-field X-ray plan with a 64 Gy mean target dose, the use of protons increases the TCP by 2% on average, but for 5 of the patients the increases are greater than 4%. The result is in general positive towards the use of protons but a few patients do not benefit from it and this indicates the importance of patient selection for maximum clinical benefit.

Humans↗
PubMed1995

The optimisation of wedge filters in radiotherapy of the prostate.

A treatment plan optimisation algorithm has been applied to 12 patients with early prostate cancer in order to determine the optimum beam-weights and wedge angles for a standard conformal three-field treatment technique. The optimisation algorithm was based on fast-stimulated-annealing using a cost function designed to achieve a uniform dose in the planning-target-volume (PTV) and to minimise the integral doses to the organs-at-risk. The algorithm has been applied to standard conformal three-field plans created by an experienced human planner, and run in three PLAN MODES: (1) where the wedge angles were fixed by the human planner and only the beam-weights were optimised; (2) where both the wedge angles and beam-weights were optimised; and (3) where both the wedge angles and beam-weights were optimised and a non-uniform dose was prescribed to the PTV. In the latter PLAN MODE, a uniform 100% dose was prescribed to all of the PTV except for that region that overlaps with the rectum where a lower (e.g., 90%) dose was prescribed. The resulting optimised plans have been compared with those of the human planner who found beam-weights by conventional forward planning techniques. Plans were compared on the basis of dose statistics, normal-tissue-complication-probability (NTCP) and tumour-control-probability (TCP). The results of the comparison showed that all three PLAN MODES produced plans with slightly higher TCP for the same rectal NTCP, than the human planner. The best results were observed for PLAN MODE 3, where an average increase in TCP of 0.73% (+/- 0.20, 95% confidence interval) was predicted by the biological models. This increase arises from a beneficial dose gradient which is produced across the tumour. Although the TCP gain is small it comes with no increase in treatment complexity, and could translate into increased cures given the large numbers of patients being referred. A study of the beam-weights and wedge angles chosen by the optimisation algorithm revealed significant inter-patient variability the implications of which are examined. Probably the most significant benefit of the algorithm is the time saved (about a factor of 10) in computing optimised beam-weights and wedge angles for this simple plan.

Algorithms↗
PubMed1990

Biphasic effects of magnesium on the [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine binding in the rat cerebral cortex.

Mg2+ at micromolar concentrations greatly enhanced [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([3H]TCP) binding to well-washed rat cortical membranes, whereas [3H]TCP binding was inhibited by Mg2+ at concentrations higher than 1 mM. In the presence of either L-glutamate (10 microM) or glycine (10 microM), 30 microM Mg2+ caused further stimulation of [3H]TCP binding, suggesting that a high-affinity site for Mg2+ is distinct from the glutamate or glycine binding site. These findings indicate that Mg2+ acts on at least two different recognition sites, e.g. a novel high-affinity site for Mg2+ which stimulates [3H]TCP binding and the Mg2+ recognition site located within the ion channel.

Animals↗
PubMed1992

Effects of glycine antagonists on Mg(2+)- and glycine-induced [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine binding.

We investigated the effects of glycine antagonists, 3-amino-1-hydroxy-2- pyrrolidone (HA-966), 7-chlorokynurenic acid (7-Cl-KYNA), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylic acid (DHQXC), 6,7-dichloroquinoxaline-2,3-dione (DCQX), and 5-chloro-indole-2-carboxylic acid (5-Cl-I2CA), on Mg(2+)- and glycine-induced [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine ([3H]TCP) binding to well-washed rat cortical membranes. Except for 5-Cl-I2CA, all the glycine antagonists completely inhibited not only glycine- but also Mg(2+)-induced [3H]TCP binding in a concentration-dependent manner. Out of all the glycine antagonists examined DHQXC most selectively inhibited Mg(2+)-induced [3H]TCP binding, while DCQX was the most selective for inhibiting glycine-induced [3H]TCP binding.

Animals↗
PubMed1995

The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice.

PURPOSE: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (Tpot) of this tumor to the effective doubling time (Teff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. METHODS AND MATERIALS: The TCP was assessed using the TCD50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The Tpot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to Teff. RESULTS: The TCD50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD50 values was significant (p < 0.05) between groups 1 and 2 (30 fractions/10 days and 30 fractions/15 days) vs. group 3 (30 fractions/30 days). The loss in TCP due to the prolongation of the overall treatment time from 10 days to 30 days was found to be 1.35-1.4 Gy/day. The pretreatment Tpot (2.4 days) was longer than the calculated Teff in groups 2 and 3 (1.35 days). CONCLUSION: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment Tpot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen.

Animals↗
PubMed1988

A Drosophila melanogaster gene encodes a protein homologous to the mouse t complex polypeptide 1.

We have isolated and sequenced a cDNA from Drosophila melanogaster that is homologous to the mouse Tcp-1 gene encoding the t complex polypeptide 1, TCP-1. The Drosophila gene maps by in situ hybridization to bands 94B1-2 of the polytene chromosomes. It shares 66% nucleotide sequence identity with the mouse gene. The predicted Drosophila protein consists of 557 amino acids and shares 72% identity with the mouse polypeptide. The TCP-1 polypeptide appears to be highly conserved in evolution from mammals to simple eukaryotes because the Drosophila gene probe also detects related sequences in DNA from the yeast, Saccharomyces cerevisiae. The presence of TCP-1-related polypeptides in organisms such as Drosophila and yeast should facilitate biochemical and genetic analysis of its function.

Amino Acid Sequence↗
PubMed1994

The toxicity of organophosphate compounds towards cultured PC12 cells.

The effects of three representative organophosphates (OPs), tricresyl phosphate (TCP), triphenyl phosphite (TPP) and paraoxon (POX) on the proliferation and viability of rat PC12 pheochromocytoma cells were studied. With respect to its IC50, TCP was at least an order of magnitude more potent in its antiproliferative activity than both TPP and POX. All test OPs were cytotoxic at concentrations inhibiting cell proliferation. No compound inhibited cell growth below 10 micrograms/ml. For TCP and TPP the estimated IC50 values from proliferation assays were lower than published LD50 values in vivo, whereas paraoxon was much less toxic in vitro than in vivo. Subcytotoxic levels of TCP (1 micrograms/ml) were found to inhibit the maintenance of neurites on cells grown in the presence of nerve growth factor.

Animals↗
PubMed1993

Monoclonal antibodies against a phencyclidine derivative are used to investigate protein-ligand interactions.

Monoclonal antibodies against the irreversible alkylator N-ethyl-1-[2-(4-isothiocyanothienyl)]cyclohexylamine (ITCE) of the 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) binding site of the N-methyl-D-aspartate receptor were raised. Each antibody was characterized in a competition enzyme-linked immunosorbent assay (ELISA) with a range of TCP analogs. It was found that each monoclonal antibody has a different affinity profile for the various TCP analogs. No correlation between the structure of the side chain groups of each compound and the selective affinities of the antibodies could be deduced, indicating that the overall affinity of the antibodies is determined by more than just the sum of the interaction forces with each ligand's functional groups. In addition to the possible identification of endogenous TCP-like compounds these antibodies could be used as a model to study the molecular interaction between drugs and their receptors' active sites.

Animals↗
PubMed2006

Surface characterisation of various bone cements prepared with functionalised methacrylates/bioactive ceramics in relation to HOB behaviour.

This study reports the relationship between the biocompatibility and surface properties of experimental bone cements. The effect of hydroxyapatite (HA) or alpha-tri-calcium phosphate (alpha-TCP) incorporated into bone cements prepared with methyl methacrylate as base monomer and either methacrylic acid or diethyl amino ethyl methacrylate (DEAEMA) as comonomers was investigated. The in vitro biocompatibility of these composite cements was assessed in terms of the interaction of primary human osteoblasts grown on the materials over a period of 5 days and compared with a control surface. These results were related to the surface properties investigated through a number of techniques, namely Fourier transform infrared, contact angle measurements, X-ray photoelectron spectroscopy and energy dispersive analysis of X-rays. Complementary techniques of thermal analysis and ion chromatography were also performed. Biocompatibility results showed that the addition of alpha-TCP improves biocompatibility regardless of comonomer type. This is in contrast to HA-based cements where cell proliferation was significantly lower. Surface characterisations showed that structural integrity of the materials was maintained in the presence of the acid and base comonomers, and water contact angles were reduced particularly in DEAEMA containing materials. Furthermore, ion chromatography confirmed higher Ca2+ and PO4(3-) ion release by both types of ceramics, particularly for those containing DEAEMA. In conclusion, the incorporation of acidic and basic comonomers to either HA or alpha-TCP ceramics containing bone cements can have differential effects upon the attachment and proliferation of bone cells in vitro. Moreover, those cements consisting of alpha-TCP and containing DEAEMA comonomer indicated the most favourable biocompatibility.

Biocompatible Materials↗
PubMed2006

Fibre reinforced bioresorbable composites for spinal surgery.

Composites containing different amounts of beta-tricalcium phosphate (beta-TCP) embedded in a poly-lactide (PLA70) matrix with and without poly-lactide (PLA96) fibre reinforcement were studied and the feasibility of using these composites in spinal fusion implants was examined. Compressive yield strength was measured in two directions: parallel to (83-97 MPa) and perpendicular to (108-123 MPa) the laminated structure of the composites. In the parallel direction, the addition of beta-TCP decreased compressive yield strength while in the perpendicular direction this was increased when compared to plain specimens (p<0.05). Fibre reinforcement had no significant effect on compressive yield strength (p<0.05), but did increase impact strength by 127-216% for notched specimens (parallel direction) and by about 65% for un-notched specimens (perpendicular direction) (p<0.05). A 24 week in vitro analysis of implant prototypes in simulated body fluid revealed a decrease in compressive yield strength, which was greater for the samples containing 50 wt.% beta-TCP than for those containing 25 wt.% beta-TCP. After 12 weeks incubation the composites retained 66-99% of their initial compressive strength, depending on composition. After 24 weeks incubation the lowest compressive strength was 51% (56 MPa: 50/50) and the highest was 94% (90 MPa: 75/25) of the initial value. Calcium phosphate precipitation on the surfaces of the materials in vitro was also observed. The initial compressive strengths of the studied composites were comparable to materials used in spinal fusion applications, but adequate strength retention behaviour needs to be confirmed before undertaking clinical experiments.

Biocompatible Materials↗
PubMed2006

Novel highly biodegradable biphasic tricalcium phosphates composed of alpha-tricalcium phosphate and beta-tricalcium phosphate.

Novel biodegradable biphasic tricalcium phosphates (BTCP) composed of alpha-tricalcium phosphate (alpha-TCP) and beta-tricalcium phosphate (beta-TCP) were successfully synthesized by heating amorphous calcium phosphate precursors with different structures at 800 degrees C for 3 h. The ratio of alpha-TCP and beta-TCP in the calcium phosphate particle can be controlled by aging time and pH value during synthesis of the amorphous precursor.

Biocompatible Materials↗