[TCP-concept in theory and practice].
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Adult↗
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[TCP - European Congress for bioimplantology and gnathology].
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Biocompatible Materials↗
Fitting tumor control probability models to biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer: pitfalls in deducing radiobiologic parameters for tumors from clinical data.
PURPOSE: The goal of tumor control probability (TCP) models is to predict local control for inhomogeneous dose distributions. All existing fits of TCP models to clinical data have utilized summaries of dose distributions (e.g., prescription dose). Ideally, model fits should be based on dose distributions in the tumor, but usually only dose-volume histograms (DVH) of the planning target volume (PTV) are available. We fit TCP models to biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer using either a dose distribution summary or the full DVH in the PTV. We discuss differences in the radiobiologic parameters and dose-response curves and demonstrate pitfalls in interpreting the results. METHODS AND MATERIAL: Two mechanistic TCP models were fit with a maximum likelihood technique to biopsy outcome from 103 prostate patients treated at Memorial Sloan-Kettering Cancer Center. Fits were performed separately for different patient subgroups defined by tumor-related prognostic factors. Fits were based both on full DVHs, denoted TCP(DVH(calc)), and, alternatively, assuming a homogeneous PTV dose given by the mean dose (Dmean) of each DVH, denoted TCP(Dmean(calc)). Dose distributions for these patients were very homogeneous with any cold spots located on the periphery of the PTV. These cold spots were uncorrelated with biopsy outcome, likely because the low-dose regions may not contain tumor cells. Therefore, fits of TCP models that are potentially sensitive to cold spots (e.g., TCP(DVH(calc))) likely give biologic parameters that diminish this sensitivity. In light of this, we examined differences in fitted clonogenic cell number, N(C), or density, rho(C), surviving fraction after 2 Gy, SF(2), or radiosensitivity, alpha, and their standard deviations in the population, sigma(SF(2)) and sigma(alpha), resulting from fits based on TCP(DVH(calc)) and TCP(Dmean(calc)). Dose-response curves for homogeneous irradiation (characterized by TCD(50), the dose for a TCP of 50%) and differences in TCP predictions calculated from the DVH using alternatively derived parameters were evaluated. RESULTS: Fits of TCP(Dmean(calc)) are better (i.e., have larger likelihood) than fits of TCP(DVH(calc)). For TCP(Dmean(calc)) fits, matching values of SF(2) and sigma(SF(2)) (or alpha and sigma(alpha)) exist for all N(C) (rho(C)) above a threshold that give fits of equal quality, with no maximum in likelihood. In contrast, TCP(DVH(calc)) fits have maximum likelihood for high SF(2) (low alpha) values that minimize effects of cold spots. Consequently, small N(C) (rho(C)) values are obtained to match the observed control rate. For example, for patients in low-, intermediate-, and high-risk groups, optimum values of SF(2) and N(C) are 0.771 and 3.3 x 10(3), 0.736 and 2.2 x 10(4), and 0.776 and 1.0 x 10(4), respectively. The TCD(50) of dose-response curves for intermediate-risk patients is 2.6 Gy lower using TCP(DVH(calc)) parameters (TCD(50) = 67.8 Gy) than for TCP(Dmean(calc)) parameters (TCD(50) = 70.4 Gy). TCP predictions calculated from the DVH using risk group-dependent TCP(Dmean(calc)) parameters are up to 53% lower than corresponding calculations with TCP(DVH(calc)) parameters. CONCLUSION: For our data, TCP parameters derived from DVHs likely do not reflect true radiobiologic parameters in the tumor, but are a consequence of the reduced importance of low-dose regions at the periphery of the PTV. Deriving radiobiologic parameters from TCP(Dmean(calc)) fits is not possible unless one parameter is already known. TCP predictions using TCP(DVH(calc)) and TCP(Dmean(calc)) parameters may differ substantially, requiring consistency in the derivation and application of model parameters. The proper derivation of radiobiologic parameters from clinical data requires both substantial dose inhomogeneities and understanding of how these coincide with tumor location.
Adenocarcinoma↗
Formation and characterization of carbon monoxide adducts of iron "twin coronet" porphyrins. Extremely low CO affinity and a strong negative polar effect on bound CO.
The carbon monoxide (CO) adducts of iron "twin coronet" porphyrins (TCPs) are characterized by UV-vis, resonance Raman (RR), IR, and 13C NMR spectroscopies. A superstructured porphyrin, designated as TCP, was used as a common framework for the four different types of iron complexes. TCP bears two binaphthalene bridges on each side and creates two hydrophobic pockets surrounded by the bulky aromatic rings. In the CO-binding cavities, the hydroxyl groups are oriented toward the center above the heme. The iron complexes investigated are as follows: TCP (which is without a covalently linked axial ligand), TCP-PY (which has a linked pyridine ligand), and TCP-TB and TCP-TG (both of which have a linked thiolate ligand). These complexes were synthesized as ferric forms and identified by the various spectroscopic methods. The UV-vis spectra of TCP-CO and TCP-PY-CO exhibit lambda(max) at 432, 546 and 428, 541 nm, respectively. On the other hand, the CO adducts of TCP-TB and TCP-TG show typical hyperporphyrin spectra for a thiolate-ligated iron(II) porphyrin-CO complex. In the RR spectra, the nu(Fe-CO) bands were observed at 506, 489 cm(-1) (TCP), 465 cm(-1) (TCP-PY), 458, 437 cm(-1) (TCP-TG) and 429 cm(-1) (TCP-TB). Compared with the reported nu(Fe-CO) frequencies of hemoproteins and their model systems, these observed values are unusually low. Further, abnormally high nu(C-O) bands are observed at 1990 cm(-1) (TCP-CO) and 2008 cm(-1) (TCP-PY-CO) in IR spectra. The lower nu(Fe-CO) and the higher nu(C-O) frequencies can be ascribed to the strong negative polar effect caused by the vicinal hydroxyl groups in the cavity. This prediction is further supported by the observation of significant 13C shieldings exhibited by TCP-CO (delta = 202.6 ppm) and TCP-PY-CO (delta = 202.3 ppm), in comparison to hemoproteins and other heme models. The CO affinity of TCP-PY (P1/2CO = 0.017 Torr at 25 C) is unusually lower than other heme models. The unique behavior of these CO adducts is discussed in context of the TCP structures.
Binding Sites↗
Phase formation and evolution in the silicon substituted tricalcium phosphate/apatite system.
The sintering of silicon doped calcium phosphate ceramics prepared from a basic colloidal hydroxyapatite (Ca5(PO4)3OH or HA) precipitate mixed with silica over 800 degrees C yields a phase mixture of tricalcium phosphate phases (TCP) designated Si-TCP, beta-TCP and a silicon substituted dehydrated apatite (Si-Ap). The Si-TCP phase is defined as a combination of a silicon stabilized TCP in which the silicon content attains a saturated value (Ca3(P0.9Si0.1O3.95)2 or Si-TCP(sat)) and alpha-TCP (Ca3(PO4)2). Si-TCP(sat) has the same crystalline space group (P2(1)/a) as alpha-TCP, but with characteristically different lattice parameters due to the substitution of silicon in tetrahedral phosphorus sites. The nucleation and growth kinetics of Si-TCP in samples of composition 0.2 mol SiO2:mol HA (0.2:1) and 1 mol SiO2:mol HA (1:1) can be understood in terms of the initial growth of alpha-TCP at a silica-HA interface followed by a transformation to Si-TCP(sat) or beta-TCP. A thermodynamic model for the formation of Si-TCP(sat) predicts a nucleation temperature of 795 degrees C, in close agreement with experiment. If sufficient silicon is available, the alpha-TCP transforms to Si-TCP(sat) during extended sintering. In the absence of sufficient silicon, the alpha-TCP transforms to beta-TCP.
Apatites↗
Effects of the electrode temperature of a new monitor, TCM4, on the measurement of transcutaneous oxygen and carbon dioxide tension.
The transcutaneous measurement of oxygen (tcP(O2)) and carbon dioxide (tcP(CO2)) tensions may serve as a surrogate of arterial oxygen (Pa(O2)) and carbon dioxide (Pa(CO2)) tensions, respectively. We investigated the effects of the electrode temperature of a new device, TCM4, on the measurement of tcP(O2) and tcP(CO2). Twenty-five patients scheduled for major lower abdominal surgery were enrolled. The electrode of the TCM4 was attached to the chest, with its temperature set to 37 degrees C, 40 degrees C, 42 degrees C, 43 degrees C, or 44 degrees C. tcP(O2), tcP(CO2), end-tidal carbon dioxide tension (Et(CO2)), Pa(O2), and Pa(CO2) were simultaneously measured at various Et(CO2) levels and inhaled oxygen concentrations. The times required for stabilization of the tcP(O2) and tcP(CO2) values were measured. A Bland-Altman plot was used to compare the two measurements. The time required for stabilization was shorter with a higher electrode temperature, but the shortest time was still more than 150 s. TcP(O2) correlated well with Pa(O2) at 43 degrees C and 44 degrees C. TcP(CO2) correlated well with Pa(CO2) and Et(CO2) at 43 degrees C. The bias and limits of agreement were larger with lower electrode temperature for TcP(O2)--Pa(O2), tcP(CO2)--Pa(CO2), and tcP(CO2)-Et(CO2). We concluded that the electrode of the TCM4 should be heated to at least 43 degrees C to measure tcP(O2) and tcP(CO2). However, the absolute values of tcP(O2) and tcP(CO2) could not be used as surrogate measurements of Pa(O2) and Pa(CO2), respectively.
Adult↗
The controlled resorption of porous alpha-tricalcium phosphate using a hydroxypropylcellulose coating.
Tricalcium phosphate (TCP) ceramic is known in orthopedics to be a bioresorbable bone substitute. A porous TCP ceramic body also has high potential as a drug delivery system in bony defects. Porous alpha-TCP ceramic can be easily fabricated using conventional sintering of beta-TCP, since alpha-TCP is the thermodynamically stable phase at temperatures above 1 100 degrees C. However, the solubility of alpha-TCP is much higher than that of beta-TCP. Therefore, the dissolution of porous alpha-TCP progresses at a higher rate than bone repair. In the present study, we attempted to reduce the dissolution rate of porous alpha-TCP by employing an organic polymer coating. We fabricated porous alpha-TCP ceramic with a continuous 10-50 microm diameter pore structure by sintering a body made from a beta-TCP and potato starch slurry. The porous body obtained was coated with hydroxypropylcellulose (HPC), and then subjected to heat treatment. The chemical durability and mechanical properties of the body were examined before and after coating with the HPC. The dissolution of porous alpha-TCP in buffered solutions was reduced by coating with HPC and drying at 60 degrees C. The compressive strength of the porous alpha-TCP was also improved by coating with HPC. The results of in vivo experiments showed that some parts of the porous alpha-TCP ceramic coated with HPC remained in the canal of the tibia of a rabbit four weeks after implantation, whereas no residual was observed in a non-coated alpha-TCP ceramic. Coating with HPC was found to be effective for controlling bioresorption and improving the workability of porous alpha-TCP ceramic. The prepared porous alpha-TCP ceramic is expected to be useful as a novel material for bone fillers by incorporating it with drugs or osteoinductive factors.
Animals↗
Regulation of cytoplasmic tubulin carboxypeptidase activity in vitro by cations and sulfhydryl-modifying compounds.
alpha-tubulin subunits within microtubules (MTs) can be post-translationally detyrosinated by a tubulin-specific carboxypeptidase (TCP) activity to form biochemically distinct MTs. Attempts to characterize and purify TCP have suffered from the inability to detect low levels of activity and to distinguish TCP from other, competing enzyme activities. We recently developed an assay for TCP [Webster et al. (1992) Biochemistry 31:5849] that uses taxol-stabilized MTs as the substrate. In this study, we exploited the increased sensitivity and specificity of this new assay to explore the effects of various agents that might act to either stimulate or inhibit this enzyme in vitro. We tested a variety of both monovalent and divalent cations for their ability to affect TCP, and tested whether the cations were affecting the enzyme, the substrate, or both. We found that TCP displayed salt-sensitive binding to MTs, characteristic of other, more well characterized MT-associated proteins. While both calcium and magnesium stimulated TCP activity over a narrow concentration range (2-10 mM), they inhibited activity at higher concentrations. Other divalent cations tested, including zinc, copper, and cobalt, inhibited TCP at virtually all concentrations tested, but to different levels (zinc > copper > cobalt). Most of the zinc-induced TCP inhibition was attributed to the interference with the normal binding of TCP to MTs. In addition, we examined the involvement of free sulfhydryl groups (which are important for the activities of many types of enzymes) in TCP activity by the addition of sulfhydryl-modifying compounds during the assay, and found that their addition reduced TCP activity mainly (but not solely) by their action on the extract that contained the TCP. Finally, we tested the ability of DL-benzylsuccinic acid, a potent inhibitor of carboxypeptidase A, to inhibit TCP. While carboxypeptidase A has been found, in other studies, to be inhibited by micromolar concentrations, TCP was affected only at concentrations above 20 mM, adding another proof that carboxypeptidase A and TCP are distinct enzyme activities.
Animals↗
N-(2-cyanoethyl)tranylcypromine, a potential prodrug of tranylcypromine: its disposition and interaction with catecholamine neurotransmitters in brain.
The disposition of the N-cyanoethyl analogue of tranylcypromine (TCP) and the TCP formed from it have been studied in the rat brain following intraperitoneal (ip) administration (0.1 mmol/kg) and the resultant data compared with those obtained following an equimolar dose of TCP. Brain concentrations of the neurotransmitter amines dopamine (DA) and noradrenaline (NA) have also been determined, as well as the percentage inhibition of monoamine oxidase (MAO) types A and B. Our results indicate that the N-cyanoethyl analogue may be a useful prodrug of TCP, providing lower but more sustained concentrations of TCP in brain. Brain levels of DA were increased in a similar pattern after CE-TCP or TCP. Brain levels of NA were decreased by TCP at most time intervals, while CE-TCP produced a much less pronounced effect. Both CE-TCP and TCP inhibited MAO-A and MAO-B, with maximum inhibition occurring 60 min after CE-TCP dosing and 30 min after dosing with TCP, times at which brain concentrations of CE-TCP and TCP were at the maximum.
Animals↗
Exposures of preschool children to chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyridinol in their everyday environments.
As part of the Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) study, we investigated the exposures of preschool children to chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyridinol (TCP) in their everyday environments. During this study, the participants were still able to purchase and apply chlorpyrifos at their homes or day care centers. Participants were recruited randomly from 129 homes and 13 day care centers in six North Carolina counties. Monitoring was performed over a 48-h period at the children's homes and/or day care centers. Samples that were collected included duplicate plate, indoor and outdoor air, urine, indoor floor dust, play area soil, transferable residues (PUF roller), and surface wipes (hand, food preparation, and hard floor). The samples were extracted and analyzed by gas chromatography/mass spectrometry. Chlorpyrifos was detected in 100% of the indoor air and indoor floor dust samples from homes and day care centers. TCP was detected at homes and day care centers in 100% of the indoor floor dust and hard floor surface wipe, in >97% of the solid food, and in >95% of the indoor air samples. Generally, median levels of chlorpyrifos were higher than those of TCP in all media, except for solid food samples. For these samples, the median TCP concentrations were 12 and 29 times higher than the chlorpyrifos concentrations at homes and day care centers, respectively. The median urinary TCP concentration for the preschool children was 5.3 ng/ml and the maximum value was 104 ng/ml. The median potential aggregate absorbed dose (ng/kg/day) of chlorpyrifos for these preschool children was estimated to be 3 ng/kg/day. The primary route of exposure to chlorpyrifos was through dietary intake, followed by inhalation. The median potential aggregate absorbed dose of TCP for these children was estimated to be 38 ng/kg/day, and dietary intake was the primary route of exposure. The median excreted amount of urinary TCP for these children was estimated to be 117 ng/kg/day. A full regression model of the relationships among chlorpyrifos and TCP for the children in the home group explained 23% of the variability of the urinary TCP concentrations by the three routes of exposure (inhalation, ingestion, dermal absorption) to chlorpyrifos and TCP. However, a final reduced model via step-wise regression retained only chlorpyrifos through the inhalation route and explained 22% of the variability of TCP in the children's urine. The estimated potential aggregate absorbed doses of chlorpyrifos through the inhalation route were low (median value, 0.8 ng/kg/day) and could not explain most of the excreted amounts of urinary TCP. This suggested that there were other possible sources and pathways of exposure that contributed to the estimated potential aggregate absorbed doses of these children to chlorpyrifos and TCP. One possible pathway of exposure that was not accounted for fully is through the children's potential contacts with contaminated surfaces at homes and day care centers. In addition, other pesticides such as chlorpyrifos-methyl may have also contributed to the levels of TCP in the urine. Future studies should include additional surface measurements in their estimation of potential absorbed doses of preschool children to environmental pollutants. In conclusion, the results showed that the preschool children were exposed to chlorpyrifos and TCP from several sources, through several pathways and routes. .
Air↗
Determination of chlorpyrifos, chlorpyrifos oxon, and 3,5,6-trichloro-2-pyridinol in rat and human blood.
Analytical methods to quantitate chlorpyrifos and two potential metabolites, chlorpyrifos oxon (oxon) and 3,5,6-trichloro-2-pyridinol (TCP), in human and rat blood are described. Chlorpyrifos and the oxon were extracted simultaneously with a methanol/hexane mixture from 0.5 mL blood that was deactivated with an acidic salt solution. The extract was then concentrated and analyzed by negative-ion chemical ionization gas chromatography-mass spectrometry (NCI-GC-MS). TCP was extracted from a separate 0.1-mL aliquot of blood, also deactivated by the addition of acid. The t-butyldimethylsilyl derivative of TCP was formed using MTBSTFA, and the analysis was performed by NCI-GC-MS. Stable isotope analogues of chlorpyrifos (-13C2-15N), oxon (-13C2-15N), and TCP (-13C2) were used as internal standards. Oxon was observed to partially degrade to TCP during the sample analysis. Accurate oxon and TCP measurements were obtained with the use of oxon-13C2-15N, TCP-13C2, and TCP-13C2-15N internal standards, which compensated for both the degradation of oxon and the formation of artifactual TCP during analysis. The limits of quantitation were 1 ng/mL blood for both chlorpyrifos and oxon and 10 ng/mL for TCP. Calibration curves were linear over the concentration range of 2.5-2500 ng/mL solvent for chlorpyrifos and oxon and between 5 and 1060 ng/mL solvent for TCP. Taking concentration factors and extraction efficiencies into account, these linear ranges represent blood concentrations of approximately 0.3-300 ng/mL blood for chlorpyrifos and the oxon and 6-1300 ng/mL blood for TCP. The lowest spike level for chlorpyrifos and the oxon was 1 ng/mL blood, and the lowest spike level for TCP was 10 ng/mL blood. Recoveries from rat blood were as follows: 106-119% for chlorpyrifos, 94-104% for oxon, and 85-102% for TCP. In addition, chlorpyrifos and oxon were incubated with rat and human blood for various time intervals before deactivation to determine precautions that needed to be taken when collecting and handling specimens. No change in chlorpyrifos concentration was observed in rat blood up to 180 min at 37 degrees C. In contrast, the oxon was rapidly hydrolyzed to TCP in both rat (t 1/2 approximately 10 s) and human (t 1/2 approximately 55 s) blood held at 37 degrees C. The hydrolysis rate for the oxon was independent of whether a rat had been administered chlorpyrifos previously, the initial oxon concentration, the presence of chlorpyrifos, and the age or gender of the human volunteers. These results suggest rapid sample preparation is critical for accurate determinations of the oxon metabolite of chlorpyrifos. These methods provide excellent tools for use in chlorpyrifos pharmacokinetic modeling studies.
Adult↗
Metabolism of the flame retardant plasticizer tris(2-chloroethyl)phosphate by human and rat liver preparations.
Previous studies indicate that tris(2-chloroethyl)phosphate (TCP) preferentially produces hippocampal brain lesions in female versus male rats, and the expression of these lesions is inversely related to the in vivo rate of TCP metabolism. In the present studies, TCP (0.17 mM in all incubations) was metabolized in vitro by liver slices and microsomes from human and Fischer 344N rat liver to bis(2-chloroethyl) hydrogen phosphate (BCP), 2-chloroethanol (CE), and three unidentified metabolites. The rate of TCP metabolism by male rat liver microsomes and liver slices was 0.049 nmol/min/mg protein and 2.53 nmol/min/g liver, respectively. TCP metabolism by male rat liver microsomes was inhibited by 10 microM diisopropyl fluorophosphate, 10 microM paraoxon and carbon monoxide. TCP did not appear to be metabolized by female rat liver microsomes, but female rat liver slices metabolized TCP at a rate of 1.51 nmol/min/g liver. TCP was metabolized by male and female rat plasma at a rate of 0.156 and 0.169 nmol/ml plasma, respectively. TCP was metabolized by male and female human liver microsomes at a rate of 0.027 and 0.031 nmol/min/mg protein, respectively. TCP was metabolized by male and female human liver slices at a rate of 1.37 and 1.82 nmol/min/g liver, respectively. BCP and CE were the major metabolites formed in all studies, except for liver slices and microsomes from two human male subjects in which an unidentified metabolite constituted 29 to 38% of the total TCP metabolism. TCP was not metabolized by plasma or whole blood from male or female human subjects. These results support the previously reported sex-specific difference in TCP metabolism by male and female Fischer 344N rats. However, no sex-specific difference in rates of TCP metabolism by male and female human liver microsomes or slices was observed.
Adult↗
alpha-Tocopheryl succinate inhibits monocytic cell adhesion to endothelial cells by suppressing NF-kappa B mobilization.
The adherence of monocytes to activated endothelium is an early event in atherogenesis. Because antioxidants have been considered to be of antiatherosclerotic potential, we investigated the effects of alpha-tocopherol (TCP) and its acetate and succinate esters on monocyte adhesion to cytokine-stimulated human umbilical vein endothelial cells (HUVEC). Endothelial cells were treated with TCP, alpha-tocopherol acetate (TCP acetate), or alpha-tocopheryl succinate (TCP succinate) before stimulation with tumor necrosis factor-alpha (TNF-alpha; 10 U/ml, 6 h) or interleukin-1 beta (IL-1 beta; 10 U/ml, 6 h). Cytokine-stimulated cell surface expression of vascular cell adhesion molecule-1 (VCAM-1, CD106) and E-selectin (ELAM-1, CD62E), but not of intercellular adhesion molecule-1 (ICAM-1, CD54), was time- and dose-dependently inhibited by TCP succinate but not by TCP or TCP acetate. TCP succinate (200 microM, 24 h) reduced TNF-induced VCAM-1 and E-selectin expression from a specific mean fluorescence intensity of 151 +/- 28 to 12 +/- 4 channels and from 225 +/- 38 to 79 +/- 21 channels, respectively. Succinate alone had no effect. Decreased adhesion molecule expression was associated with a reduction of monocytic cell adhesion. TCP succinate (20 microM, 72 h), but not TCP (200 microM, 72 h), reduced U-937 cell adhesion to TNF-alpha-stimulated (10 U/ml, 6 h) HUVEC by 30% (P < 0.025) and to IL-1 beta-stimulated HUVEC by 56% (P < 0.010). Electrophoretic mobility-shift assays of HUVEC nuclear proteins revealed a decrease in TNF-alpha-stimulated nuclear factor-kappa B (NF-kappa B) activation after pretreatment of HUVEC with TCP succinate but not with TCP, TCP acetate, or succinate alone. In conclusion, we demonstrate that the vitamin E derivative TCP succinate prevents monocytic cell adhesion to cytokine-stimulated endothelial cells by inhibiting the activation of NF-kappa B, further emphasizing the antiatherosclerotic potential of lipid soluble antioxidants.
Biological Transport↗
Anterior lumbar interbody fusion with carbon fiber cage loaded with bioceramics and platelet-rich plasma. An experimental study on pigs.
Platelet-rich plasma (PRP) is an autogenous source of growth factor and has been shown to enhance bone healing both in clinical and experimental studies. PRP in combination with porous hydroxyapatite has been shown to increase the bone ingrowth in a bone chamber rat model. The present study investigated whether the combination of beta tricalcium phosphate (beta-TCP) and PRP may enhance spinal fusion in a controlled animal study. Ten Danish Landrace pigs were used as a spinal fusion model. Immediately prior to the surgery, 55 ml blood was collected from each pig for processing PRP. Three-level anterior lumbar interbody fusion was performed with carbon fiber cages and staples on each pig. Autogenous bone graft, beta-TCP, and beta-TCP loaded with PRP were randomly assigned to each level. Pigs were killed at the end of the third month. Fusion was evaluated by radiographs, CT scanning, and histomorphometric analysis. All ten pigs survived the surgery. Platelet concentration increased 4.4-fold after processing. Radiograph examination showed 70% (7/10) fusion rate in the autograft level. All the levels with beta-TCP+PRP showed partial fusion, while beta-TCP alone levels had six partial fusions and four non-fusions ( P=0.08). CT evaluation of fusion rate demonstrated fusion in 50% (5/10) of the autograft levels. Only partial fusion was seen at beta-TCP levels and beta-TCP+PRP levels. Histomorphometric evaluation found no difference between beta-TCP and beta-TCP+PRP levels on new bone volume, remaining beta-TCP particles, and bone marrow and fibrous tissue volume, while the same parameters differ significantly when compared with autogenous bone graft levels. We concluded from our results in pigs that the PRP of the concentration we used did not improve the bone-forming capacity of beta-TCP biomaterial in anterior spine fusion. Both beta-TCP and beta-TCP+PRP had poorer radiological and histological outcomes than that of autograft after 3 months.
Animals↗
Regulation of cytoplasmic tubulin carboxypeptidase activity during neural and muscle differentiation: characterization using a microtubule-based assay.
A cycle of posttranslational modification of alpha-tubulin has previously been described in higher eukaryotes, in which a C-terminal tyrosine residue is removed and replaced by two complementary cytoplasmic enzymes. The activity of the detyrosinating enzyme, tubulin carboxypeptidase (TCP), and its potential for regulating the level of detyrosinated (Glu) subunits in microtubules (MTs) is of great interest, since TCP catalyzes the primary modification of tubulin and since the level of Glu alpha-tubulin in MTs increases during a variety of differentiative and morphogenetic events. As a first step in examining the role of TCP in cellular morphogenesis, it was necessary to develop an assay for TCP with sufficient sensitivity and specificity to detect TCP activity during these events. Unlike previously described assays for TCP, ours makes use of the affinity TCP exhibits for MTs. NGF-induced neurite outgrowth in PC-12 cells was accompanied by a moderate (approximately 2-fold) increase in TCP activity, while myogenesis of L6 cells resulted in an almost insignificant decrease in activity. Measurements of TCP activity during differentiation were correlated with the level of extract Tyr tubulin, which increased (approximately 37%) during neurite outgrowth and was unchanged during myogenic differentiation. Our results suggest that TCP activity is regulated relative to its substrate, Tyr tubulin, and that changes in MT dynamics, rather than enzymatic activities, are the primary determinants of MT posttranslational modification state during differentiation. In addition, the assay we have devised for TCP and the characterization of TCP during differentiation may allow the future delineation of the mechanism(s) of regulation of TCP and the role this enzyme plays in modulating MT function during differentiation.
Adrenal Gland Neoplasms↗
Enhanced photodegradation of 2,4,6-trichlorophenol over palladium phthalocyaninesulfonate modified organobentonite.
This article explores a supported photocatalyst of palladium(II) phthalocyaninesulfonate (PdPcS) onto organoclay for removal of 2,4,6-trichlorophenol (TCP) from water under visible light (lambda > or = 450 nm) irradiation. The composite clay was not only a good sorbent for uptake of TCP from water, but it also exhibited notable activity for TCP oxidation via singlet molecular oxygen, generated in situ from PdPcS photosensitization. Complete dechlorination of TCP could be achieved after TCP was totally oxidized. The initial rate of TCP degradation was observed to increase with the initial amount of TCP sorption, the kinetics following well the Langmuir-Hinshelwood equation. The resulting rate constant of TCP oxidation was found to increase with the alkyl chain length of the intercalated surfactant from dodecyltrimethylammonium to cetyltrimethylammonium and to octadecyltrimethylammonium. Such the trend in photoactivity was in agreement with the catalyst capacity for TCP sorption from aqueous medium. The result showed that enrichment of toxic TCP on the catalyst was indeed an efficient way for enhancement of the photosensitized degradation of target pollutant. However, PdPcS loading led to a notable decrease in TCP sorption, because of partial blocking of the sorptive sites. The optimal loading of PdPcS was about 1.0 wt %. The catalyst was characterized by nitrogen adsorption, X-ray diffraction, visible diffuse reflectance spectroscopy, and TCP sorption, which revealed that the incorporated PdPcS, mainly in the form of photoactive monomer, coexisted with the intercalated surfactant in the bentonite interlayers. Seven repeated experiments demonstrated that the composite clay was relatively stable and could be repeatedly used for sorption and degradation of TCP pollutant via molecular oxygen and visible light.
Journal Article↗
Evaluation of the hazards of industrial exposure to tricresyl phosphate: a review and interpretation of the literature.
Commercial tricresyl phosphate (TCP) is a heterogeneous mixture of isomers and aryl phosphate congeners, known for many years to induce delayed neurotoxicity (OPIDN) in humans and experimental animals. In the past the isomer tri-o-cresyl phosphate (TOCP) was thought to be the component primarily responsible for OPIDN. It is now clear that other constituents, particularly the mono-o-esters, are not only neurotoxic but also may be more potent than pure TOCP. As a generality, the toxicity potential of a particular brand of TCP is related to its content of o-phenolic residues, whereby the maximal potential is reached when o-phenolics are 33% of the mix. Historically, human TCP toxicity has resulted from inadvertent or intentional contamination of foodstuffs or beverages. TCP products with high ortho-residues synthesized by older manufacturing methods were involved in most of these cases, and were likely much more neurotoxic milligram for milligram than TOCP. Because of the great variability of TCP products, there are no conventional workplace exposure standards. Based upon data from the hen and cat, estimated human safe exposure rates for pure TOCP are estimated to be 2.5 mg/kg for a single dose, and 0.13 mg/kg/d for repetitive exposures. These levels may also be applied to TCP when o-methyl-phenyl, o-ethyl-phenyl, and o-xylenyl components are appropriately limited during manufacture such that the TCP product is less neurotoxic than TOCP. There have been relatively few reports of toxicity associated with the manufacture or use of TCP in commerce and industry. Low vapor pressures of the constituents preclude the presence of significant quantities of TCP vapor in the atmosphere. A lubricant or other formulation containing TCP may appear in the air as a mist. By these criteria the U.S. Petroleum Oil Mist exposure standard is protective when the formulation contains 4% or less of low ortho-TCP. Exposure calculations indicate that estimated safe levels are not likely to be exceeded in the well-regulated workplace. If it is of short duration, even a heavy fog of oil particulate may not exceed the 8-h-average inhalation exposure standard. Modern manufacturing practices tend to minimize the ortho content and thus the toxicity of TCP. Because individual TCP brands and synthesis methods vary, manufacturers should be consulted concerning the properties of their individual products.
Animals↗
Degradation of 2,4,6-trichlorophenol by Azotobacter sp. strain GP1.
A bacterium which utilizes 2,4,6-trichlorophenol (TCP) as a sole source of carbon and energy was isolated from soil. The bacterium, designated strain GP1, was identified as an Azotobacter sp. TCP was the only chlorinated phenol which supported the growth of the bacterium. Resting cells transformed monochlorophenols, 2,6-dichlorophenol, and 2,3,6-trichlorophenol. Phenol and a number of phenolic compounds, including 4-methylphenol, all of the monohydroxybenzoates, and several dihydroxybenzoates, were very good carbon sources for Azotobacter sp. strain GP1. The organism utilized up to 800 mg of TCP per liter; the lag phase and time for degradation, however, were severely prolonged at TCP concentrations above 500 mg/liter. Repeated additions of 200 mg of TCP per liter led to accelerated degradation, with an optimum value of 100 mg of TCP per liter per h. TCP degradation was significantly faster in shaken than in nonshaken cultures. The optimum temperature for degradation was 25 to 30 degrees C. Induction studies, including treatment of the cells with chloramphenicol prior to TCP or phenol addition, revealed that TCP induced TCP degradation but not phenol degradation and that phenol induced only its own utilization. Per mol of TCP, 3 mol of Cl- was released. 2,6-Dichloro-p-benzoquinone was detected in the resting-cell medium of Azotobacter sp. strain GP1. By chemical mutagenesis, mutants blocked in either TCP degradation or phenol degradation were obtained. No mutant defective in the degradation of both phenols was found, indicating separate pathways for the dissimilation of the compounds. In some of the phenol-deficient mutants, pyrocatechol was found to accumulate, and in some of the TCP-deficient mutants, 2,6-dichlorohydroquinone was found to accumulate.
Azotobacter↗