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PubMed2002

Inclusion of geometric uncertainties in treatment plan evaluation.

PURPOSE: To correctly evaluate realistic treatment plans in terms of absorbed dose to the clinical target volume (CTV), equivalent uniform dose (EUD), and tumor control probability (TCP) in the presence of execution (random) and preparation (systematic) geometric errors. MATERIALS AND METHODS: The dose matrix is blurred with all execution errors to estimate the total dose distribution of all fractions. To include preparation errors, the CTV is randomly displaced (and optionally rotated) many times with respect to its planned position while computing the dose, EUD, and TCP for the CTV using the blurred dose matrix. Probability distributions of these parameters are computed by combining the results with the probability of each particular preparation error. We verified the method by comparing it with an analytic solution. Next, idealized and realistic prostate plans were tested with varying margins and varying execution and preparation error levels. RESULTS: Probability levels for the minimum dose, computed with the new method, are within 1% of the analytic solution. The impact of rotations depends strongly on the CTV shape. A margin of 10 mm between the CTV and planning target volume is adequate for three-field prostate treatments given the accuracy level in our department; i.e., the TCP in a population of patients, TCP(pop), is reduced by less than 1% due to geometric errors. When reducing the margin to 6 mm, the dose must be increased from 80 to 87 Gy to maintain the same TCP(pop). Only in regions with a high-dose gradient does such a margin reduction lead to a decrease in normal tissue dose for the same TCP(pop). Based on a rough correspondence of 84% minimum dose with 98% EUD, a margin recipe was defined. To give 90% of patients at least 98% EUD, the planning target volume margin must be approximately 2.5 Sigma + 0.7 sigma - 3 mm, where Sigma and sigma are the combined standard deviations of the preparation and execution errors. This recipe corresponds accurately with 1% TCP(pop) loss for prostate plans with clinically reasonable values of Sigma and sigma. CONCLUSION: The new method computes in a few minutes the influence of geometric errors on the statistics of target dose and TCP(pop) in clinical treatment plans. Too small margins lead to a significant loss of TCP(pop) that is difficult to compensate for by dose escalation.

Algorithms↗
PubMed1980

In vitro inhibition of vitamin K dependent carboxylation by tetrachloropyridinol and the imidazopyridines.

The compounds 2,3,5,6-tetrachloro-4-pyridinol (TCP) and the structurally related imidazopyridines (IP) cause hemorrhage and lower the plasma prothrombin level in animals. In vitro, TCP and the IP are more potent inhibitors of both the vitamin K dependent carboxylase which catalyzes the posttranslational gamma-carboxylation of specific glutamyl residues in proteins and the related vitamin K epoxidase activity than they are either of vitamin K epoxide reductase or of NAD-(P)H-K oxidoreductase. TCP and IP, as is the case with the coumarin and indandione anticoagulants, are competitive inhibitors of NAD(P)H-K oxidoreductae with respect to NADH. The epoxide reductase from coumarin-resistant rats is quite resistant to inhibition not only by warfarin but also by the IP, and to a lesser extent by TCP. When interpreted in light of published in vivo experiments, the data suggest that the principal site of anticoagulant action of the IP, but not TCP, is the epoxide reductase. The anticoagulant effect of TCP may be inhibition of the carboxylase itself. TCP is a significantly more potent inhibitor of the carboxylase and epoxidase than the IP; it inhibits both the enzymatic activities to the same degree with 50% inhibition observed at about 10(-5) M. Inhibition of the carboxylase by TCP is not competitive with respect to the pentapeptide substrate phenylalanyl-leucylglutamylglutamylleucine nor with respect to the following components of the in vitro carboxylase assay: imidazole, pyridoxal 5'-phosphate, dithiothreitol, KCl, sodium bicarbonate, oxygen, and vitamin K. The order of addition of components of the assay relative to the addition of inhibitor did not affect the degree of inhibition. Inhibition is readily reversed in experiments designed to dissociate an enzyme-inhibitor complex. Analysis of double-inhibitor experiments suggests that TCP and IP have the same binding site on the carboxylase.

Animals↗
PubMed2005

Angiogenesis and hypoxia in lymph node metastases is predicted by the angiogenesis and hypoxia in the primary tumour in patients with breast cancer.

Hypoxia and angiogenesis are important factors in breast cancer progression. Little is known of hypoxia and angiogenesis in lymph node metastases of breast cancer. The aim of this study was to quantify hypoxia, by hypoxia-induced marker expression levels, and angiogenesis, by endothelial cell proliferation, comparing primary breast tumours and axillary lymph node metastases. Tissue sections of the primary tumour and a lymph node metastasis of 60 patients with breast cancer were immunohistochemically stained for the hypoxia-markers carbonic anhydrase 9 (CA9), hypoxia-inducible factor-1alpha (Hif-1alpha) and DEC-1 and for CD34/Ki-67. Endothelial cell proliferation fraction (ECP%) and tumour cell proliferation fraction (TCP%) were assessed. On haematoxylin-eosin stain, the growth pattern and the presence of a fibrotic focus were assessed. Hypoxia-marker expression, ECP% and TCP% in primary tumours and in lymph node metastases were correlated to each other and to clinico-pathological variables. Median ECP% and TCP% in primary tumours and lymph node metastases were comparable (primary tumours: ECP%=4.02, TCP%=19.54; lymph node metastases: ECP%=5.47, TCP%=21.26). ECP% correlated with TCP% (primary tumours: r=0.63, P<0.001; lymph node metastases: r=0.76, P<0.001). CA9 and Hif-1alpha expression were correlated (primary tumours P=0.005; lymph node metastases P<0.001). In primary tumours, CA9 and Hif-1alpha expression were correlated with DEC-1 expression (P=0.05), presence of a fibrotic focus (P<0.007) and mixed/expansive growth pattern (P<0.001). Primary tumours and lymph node metastases with CA9 or Hif-1alpha expression had a higher ECP% and TCP% (P<0.003); in primary tumours, mixed/expansive growth pattern and fibrotic focus were characterised by higher ECP% (P=0.03). Furthermore, between primary tumours and lymph node metastases a correlation was found for ECP%, TCP%, CA9 and Hif-1alpha expression (ECP% r=0.51, P<0.001; TCP r=0.77, P<0.001; CA9 and Hif-1alpha P<0.001). Our data demonstrate that the growth of breast cancer lymph node metastases is angiogenesis dependent and that angiogenesis and hypoxia in the primary tumour predict angiogenesis and hypoxia in the lymph node metastases. Together with previous findings in breast cancer liver metastases, which grow in 96% of cases angiogenesis independently, these data suggest that both the intrinsic growth characteristics and angiogenic potential of breast cancer cells and the site-specific tumour microenvironment determine angiogenesis and hypoxia in breast cancer.

Adult↗
PubMed1996

No evidence of a higher risk of progression to AIDS in patients with HIV-1-related severe thrombocytopenia.

The prognostic role of platelet (PLT) counts was evaluated in a cohort of 1,533 HIV-1-infected subjects followed for a median of 21 months. Thrombocytopenia (TCP), defined as a PLT count < or = 100 x 10(9)/L was present at enrollment in 11.2% of cases, with counts < or = 50 x 10(9)/L (severe TCP) in 5.3%. With the subjects with normal PLT counts (PLT >150 x 10(9)/L) as the reference group, the relative risk of developing acquired immunodeficiency syndrome (AIDS) was 0.8 [95% confidence interval (CI) 0.5-1.3, p = 0.4] for subjects with severe TCP, 2.1 (95% CI 1.4-3.1, p = 0.002) for those with PLT counts ranging from 51 to 100 x 10(9)/L (moderate TCP), and 1.6 (95% CI 1.2-2.1, p = 0.0004) for those with borderline PLT values (PLT ranging from 101 to 150 x 10(9)/L). Most of the risk increase associated with moderate TCP and borderline PLT values was explained by a higher prevalence of subjects with an older age and lower CD4+ cell counts. However, at multivariable analysis considering age, sex, risk group, and zidovudine (ZDV) treatment, the risk for subjects with severe TCP remained significantly lower than that for subjects with moderate TCP and borderline values. These results suggest the existence of different types of HIV-1-associated TCP and also suggest that severe TCP (which often arises in the early phases of infection) is not related to disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Anaerobic transformation and toxicity of trichlorophenols in a stable enrichment culture.

The transformation and toxicity of trichlorophenols (TCPs) were studied with a methanogenic enrichment culture derived from sewage sludge. Transformation of TCPs rapidly resumed after heating of the culture at *) degrees C for 1 h, suggesting that the dechlorinating bacteria are spore-forming anaerobes. 2,4,6-TCP was rapidly dechlorinated via 2,4-dichlorophenol to 4-chlorophenol. During the transformation of 2,4,6-TCP, the most probable number of dechlorinating bacteria increased by 4 orders of magnitude. The most extensive dechlorination was observed in media with complex carbon sources such as yeast extract, peptone, and Casamino Acids, but glucose, galactose, and lactose were also used by the consortium. Experiments using chloramphenicol indicated that the reductive dechlorination of 2,4,6-TCP was regulated by an inducible enzyme system. The highest initial concentration at which dechlorination of 2,4,6-TCP was observed was 400 microM. 2,4,5-TCP and 3,4,5-TCP were dechlorinated to, respectively, 3,4-dichlorophenol and 3-chlorophenol at initial concentrations of less than or equal to 40 microM. Toxicity for the acid-producing and methanogenic bacteria in the consortium was a function of chemical structure, as the inhibition of these activities increased from 2,4,6-TCP, via 2,4,5-TCP, to 3,4,5,-TCP.

Biotransformation↗
PubMed2001

Anti-class II monoclonal antibody-targeted Vibrio cholerae TcpA pilin: modulation of serologic response, epitope specificity, and isotype.

Toxin-coregulated pilus (TCP) is a colonization factor required for cholera infection. It is not a strong immunogen when delivered in the context of whole cells, yet pilus subunits or TcpA derivative synthetic peptides induce protective responses. We examined the efficacy of immunizing mice with TCP conjugated to anti-class II monoclonal antibodies (MAb) with or without the addition of cholera toxin (CT) or anti-CD40 MAb to determine if the serologic response to TcpA could be manipulated. Anti-class II MAb-targeted TCP influenced the anti-TCP peptide serologic response with respect to titer and isotype. Responses to TcpA peptide 4 were induced with class II MAb-targeted TCP and not with nontargeted TCP. Class II MAb-targeting TcpA reduced the response to peptide 6 compared to the nontargeted TCP response. Class II MAb-targeted TcpA, if delivered with CT, enhanced the serologic response to TcpA peptides. The effectiveness of the combination of targeted TCP and CT was reduced if anti-CD40 MAb were included in the primary immunization. These data establish the need to understand the role of TCP presentation in the generation of B-cell epitopes in order to optimize TcpA-based cholera vaccines.

Adjuvants, Immunologic↗
PubMed1997

Purification and characterization of 2,4,6-trichlorophenol-4-monooxygenase, a dehalogenating enzyme from Azotobacter sp. strain GP1.

The enzyme which catalyzes the dehalogenation of 2,4,6-trichlorophenol (TCP) was purified to apparent homogeneity from an extract of TCP-induced cells of Azotobacter sp. strain GP1. The initial step of TCP degradation in this bacterium is inducible by TCP; no activity was found in succinate-grown cells or in phenol-induced cells. NADH, flavin adenine dinucleotide, and O2 are required as cofactors. As reaction products, 2,6-dichlorohydroquinone and Cl- ions were identified. Studies of the stoichiometry revealed the consumption of 2 mol of NADH plus 1 mol of O2 per mol of TCP and the formation of 1 mol of Cl- ions. No evidence for membrane association or for a multicomponent system was obtained. Molecular masses of 240 kDa for the native enzyme and 60 kDa for the subunit were determined, indicating a homotetrameric structure. Cross-linking studies with dimethylsuberimidate were consistent with this finding. TCP was the best substrate for 2,4,6-trichlorophenol-4-monooxygenase (TCP-4-monooxygenase). The majority of other chlorophenols converted by the enzyme bear a chloro substituent in the 4-position. 2,6-Dichlorophenol, also accepted as a substrate, was hydroxylated in the 4-position to 2,6-dichlorohydroquinone in a nondehalogenating reaction. NADH and O2 were consumed by the pure enzyme also in the absence of TCP with simultaneous production of H2O2. The NH2-terminal amino acid sequence of TCP-4-monooxygenase from Azotobacter sp. strain GP1 revealed complete identity with the nucleotide-derived sequence from the analogous enzyme from Pseudomonas pickettii and a high degree of homology with two nondehalogenating monooxygenases. The similarity in enzyme properties and the possible evolutionary relatedness of dehalogenating and nondehalogenating monooxygenases are discussed.

Amino Acid Sequence↗
PubMed1995

Toxic effects of butylated triphenyl phosphate-based hydraulic fluid and tricresyl phosphate in female F344 rats.

Triaryl phosphates, including tricresyl phosphate (TCP and butylated triphenyl phosphates (BTP), are used in the commercial manufacture of plastics, lubricants, and hydraulic fluids. Recent reports implicate these compounds as endocrine and reproductive toxicants that can cause cholesteryl lipidosis in adrenocortical (AC) and ovarian interstitial (OI) cells, suggesting altered metabolism of steroid hormones or cholesterol or of both. We investigated potential mechanisms of BTP and TCP toxicity to determine if there were functional abnormalities of the adrenal cortex or ovary. Groups of intact (nine or 12) and ovariectomized (six) female F344 rats, 10-12 weeks of age, received 0, 0.4 g/kg TCP, or 1.7 g/kg BTP in sesame oil vehicle or 1.7 g/kg neat BTP for 20, 40, or 60 days. All rats administered BTP and TCP developed cholesteryl lipidosis in AC and OI cells; the TCP-treated group was most severely affected. Serum concentrations of androstenedione and corticosterone were unchanged, but estradiol levels were significantly (P < or = 0.05) elevated in BTP- and TCP-treated groups (14.5 times and 37.5 times greater than controls, respectively). Vaginal cytology revealed that BTP- but not TCP-treated females had abnormal reproductive cycles that were significantly prolonged in diestrus (3 times greater than control). There were significant elevations in serum total cholesterol (TCP-treated group was 1.3 times greater than controls), low-density lipoprotein (TCP-treated group was 1.8 times greater than controls), alanine transaminase (BTP-treated group was 2 times greater than controls), and albumin (a major serum estradiol-binding protein; BTP-treated group was 4.6 g/dl vs. 3.6 g/dl for controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1976

Studies of connections between locus coeruleus and cerebral cortex.

Small tracking electrodes were inserted into the cat locus coeruleus (LC), and the effects of LC stimulation were determined on the transcallosal potential (TCP) evoked in cerebral cortex on the same side. LC stimulation at 8 volts inhibited TCP amplitude an average of 11%. Rostral LC placements appeared most effective. LC stimulation, without drugs, did not affect the peak latency of the TCP. dl-Propranolol and FLA-63 blocked LC inhibition of the TCP and also increased TCP amplitude per se. Propranolol first increased the latency of the TCP during LC stimulation, then decreased decreased it, while also prolonging the latency of the TCP per se. Phenoxybenzamine increased rather than blocked the LC inhibitory effect and also increased TCP amplitude. dl-Erythro-DOPS slightly increased the LC inhibitory effect, and substantially increased TCP amplitude. dl-Threo-DOPS produced somnolence in unanesthetized animals, led to increased norepinephrine levels in cortex and brain stem, and caused cortical potentials to fluctuate widely. A midbrain lesion of the dorsal ascending NE bundle blocked the LC inhibitory effect. LC stimulation alone, or in combination with evoked cortical stimulation, did not affect the interstimulus electrocorticogram or the heart rate. In the transcallosal system of the cortical regions studied, the LC appears to play mainly an inhibitory role.

Animals↗
PubMed1999

Characterization and hormonal modulation of immunoreactive thiamin carrier protein secreted by adult rat Leydig cells in vitro.

Leydig cells isolated from adult rats and maintained under defined conditions in culture secrete a protein of molecular weight (Mr) 70 000 which is immunologically similar to chicken thiamin carrier protein (TCP). Synthesis of immunoreactive TCP by these cells is demonstrated by immunoprecipitation of [35S]methionine incorporated, newly synthesized proteins with monoclonal and polyclonal antibodies to chicken TCP. The amount of immunoreactive TCP secreted into the culture supernatant is quantitated by using a specific radioimmunoassay. Under the influence of LH, secretion of immunoreactive TCP is enhanced 3-fold and can be inhibited by up to 70% with aromatase inhibitor (1,4,6-androstatrien-3,17-dione). Cyclic AMP acts as a second messenger in the sequence of events involved in LH-induced elevation of immunoreactive TCP in Leydig cells. The effects of exogenous estradiol-17beta and diethylstilbestrol are comparable in terms of stimulation of secretion of immunoreactive TCP by these cells. Tamoxifen brought about a 70% decrease in the elevated levels of immunoreactive TCP. These results suggest that estrogen mediates immunoreactive TCP induction in hormonally stimulated adult rat Leydig cells.

Animals↗
PubMed1993

Thienylphencyclidine protection for the spinal cord of adult rats against extension of lesions secondary to a photochemical injury.

The purpose of this study was to evaluate treatment with the N-methyl-D-aspartate antagonist thienyl-phencyclidine (TCP) after spinal cord injury for its behavioral, electrophysiological, morphological, and immunohistochemical effects. Five minutes after a photochemical lesion was produced in rats at the T-8 level, the animals received TCP (1 mg/kg, intravenously) or TCP vehicle (saline). The animals were evaluated on Day 18 for neurological recovery by testing motor and sensory functions. The TCP-treated group showed less neurological impairment than the untreated group (p < 0.05 for inclined-plane stability and withdrawal reflex to extension). Somatosensory evoked potential testing was performed on Days 21 to 23 and the wave amplitude between the onset and P1 in the TCP-treated group was higher than in the untreated group (p < 0.05). Mean arterial blood pressure was not significantly modified after TCP injection. Morphometric studies of the lesion area in cross section revealed a significantly reduced spinal cord infarction in the TCP-treated group (p < 0.05). Immunohistochemical evaluation of the spinal cord in lumbar area showed an increased level of serotonin immunoreactivity in the dorsal horn of animals treated by TCP. These results demonstrate the efficacy of TCP in reducing secondary lesions after spinal cord injury in rats.

Animals↗
PubMed1991

[Clinical significance of thrombocytopenia associated with hemorrhagic cerebrovascular diseases].

We investigated the clinical significance of thrombocytopenia (platelet counts less than 10 x 10(4)/mm3) associated with hemorrhagic cerebrovascular disease. This study was conducted in 96 patients suffering from hemorrhagic cerebrovascular diseases. We divided the clinical course into 3 stages: acute (from the 1st to 7th day), subacute (8th-21st day) and chronic (after the 22nd day). The average age of the patients with thrombocytopenia (TCP) was 60.6 years old. TCP was more frequent in men (81.3%) than in women (18.7%). TCP developed in 18.6% (8/43) of patients with subarachnoid hemorrhage (SAH) and in 15.1% (8/53) of those with intracerebral hemorrhage (ICH). Among the patients with SAH, four were in the acute stage, three in the subacute stage and two in the chronic stage. TCP due to SAH was more likely to develop in the acute and/or subacute stage. TCP due to SAH showed two peak appearances: the first was within 24 hours (n = 3), and the second was around 10 days after onset (n = 3). The cause of TCP in its late peak appearance was presumed to be the consumption of platelets due to microembolism induced by vasospasm and/or hemodilution therapy. Among patients with ICH, five cases were in the acute stage, three in the subacute stage and two in the chronic stage. TCP due to ICH was more likely to develop in the acute stage. Fifty percent (4/8) of the patients with ICH had TCP on admission. This data suggested that TCP was possibly a cause or an inducer for ICH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Histopathologic study on the application of synthetic hydroxyapatite and alpha-tricalcium phosphate for vital pulpotomy].

Hydroxyapatite (HAp) and alpha-Tricalcium phosphate (alpha-TCP) are generally known as materials biocompatible to human tissue. In this study, the adaptation of HAp and alpha-TCP as a pulpotomy agent was studied histopathologically. In this study, HAp granules with a sintering temperature of 1,200 degrees C and sieved through a 37 micron sieve, and APATITE LINER TYPE I (Sankin CO.) as alpha-TCP were used. Calcium hydroxide served as a control. The physical properties of these experimental materials were evaluated and the reaction of pulp tissue to the materials was examined histolongically in dogs. alpha-TCP mixed with saline solution showed more homogeneous and higher viscosity than HAp mixed with saline solution. When alpha-TCP was applied on the site of exposure of a pulp following pulpotomy, the mechanically harmed pulp tissue was healed earlier than when HAp was applied. A hard tissue was formed earliest when calcium hydroxide was used, and then in the order of alpha-TCP and HAp. When HAp was applied, osteodentin was formed and when alpha-TCP was applied, dentin was formed on the site of exposure of a pulp following pulpotomy. When HAp or alpha-TCP was applied, the calcification in the initial stage was not observed. The calcification in initial stage was observed when calcium hydroxide was applied. These results suggest that alpha-TCP is useful as a pulpotomy agent.

Animals↗
PubMed1989

[Bone inductive activity of bone morphogenetic protein combined to beta-tricalcium phosphate].

For the development of a new delivery system for bone morphogenetic protein (BMP), BMP was bound to beta-tricalcium phosphate (beta-TCP). Powder beta-TCP was synthesized from calcium hydrogenphosphate and calcium carbonate by the dry process method to make the best use of the advantages of the BMP, which show good bone inductive activity on the surface and enhancement of new tissue by reducing the area that the implant material occupies. The beta-TCP + BMP complex and beta-TCP for the controls only were implanted in the muscle pouches of mice. Three weeks later new bone formation was observed on the exterior surface of beta-TCP + BMP complex but not of beta-TCP controls. The bone inductive activity of the beta-TCP + BMP complex is better than the BMP alone. The histological relation between the original tissue and the newly induced bone formation was normal and that of new bone and beta-TCP was also good. Consequently, the beta-TCP + BMP complex has good histocompatibility when implanted.

Animals↗
PubMed1997

Surface instability of calcium phosphate ceramics in tissue culture medium and the effect on adhesion and growth of anchorage-dependent animal cells.

The surface of biocompatible ceramics made of synthesized hydroxyapatite (HAP) and beta-tricalcium phosphate (TCP) was found to be extremely active in tissue culture medium. Using mixed ceramics of HAP and TCP which had been prepared with different Ca/P molar ratios adjusted in stepwise fashion to values of 1.50, 1.55, 1.60, 1.64 and 1.67, the characteristics of the surface were investigated. The time-dependent variation of zeta potential of the TCP-HAP ceramics immersed in distilled water and in culture medium with and without addition of fetal bovine serum showed that the surface was unstable with significant changes in the charge being observed. Dry TCP powder had a zeta potential of -19 mV, which shifted to -7 mV after soaking in water and to -26 mV in culture medium. In contrast, HAP had a zeta potential of -11 mV in a dry state, -9 mV in water and -29 mV in culture medium. Concentrations of calcium and phosphate dissolved in distilled water showed the solubility was higher for TCP than for HAP. In comparison, it was found that dissolved calcium and phosphate in the medium were removed from the solution by deposition on immersed TCP-HAP ceramics. These results suggested that the stability of the surface was closely related to both reactions of association and dissociation of calcium and phosphate in tissue culture medium. The zeta potential analysis also suggested that Ca-deficient HAP, which has a similar crystal structure to HAP with a Ca/P ratio less than 1.67, was generated by degradation and reforming of the surface layer. The most stable structure which was the most suitable for adhesion of L-929 cells was obtained by the mixture of 20% TCP and 80% HAP ceramics. In conclusion, the stability of the surface structure was considered to be the dominant factor for the enhancement of the adhesiveness of cells on TCP-HAP ceramics.

Animals↗
PubMed2003

Iron twin-coronet porphyrins as models of myoglobin and hemoglobin: amphibious electrostatic effects of overhanging hydroxyl groups for successful CO/O2 discrimination.

Inspired by the observation of polar interactions between CO and O(2) ligands and the peptide residues at the active site of hemoglobin and myoglobin, we synthesized two kinds of superstructured porphyrins: TCP-IM, which contains a linked imidazole ligand, and TCP-PY, which contains a linked pyridine ligand, and examined the thermodynamic, kinetic, and spectroscopic (UV/Vis, IR, NMR, and resonance Raman) properties of their CO and O(2) complexes. On both sides of each porphyrin plane, bulky binaphthyl bridges form hydrophobic cavities that are suitable for the binding of small molecules. In the proximal site, an imidazole or pyridine residue is covalently fixed and coordinates axially to the central iron atom. In the distal site, two naphtholic hydroxyl groups overhang toward the center above the heme. The CO affinities of TCPs are significantly lower than those of other heme models. In contrast, TCPs have moderate O(2) binding ability. Compared with reported model hemes, the binding selectivity of O(2) over CO in TCP-IM and TCP-PY complexes is greatly improved. The high O(2) selectivity of the TCPs is mainly attributable to a low CO affinity. The comparison of k(on)(CO) values of TCPs with those of unhindered hemes indicates the absence of steric hindrance to the intrinsically linear CO coordination to Fe(II) in TCP-IM and TCP-PY. The abnormally large k(off)(CO) values are responsible for the low CO affinities. In contrast, k(off)(O(2)) of TCP-PY is smaller than those of other pyridine-coordinated model hemes. For the CO adducts of TCPs, unusually low nu(Fe-CO) and unusually high nu(C-O) frequencies are observed. These results can be ascribed to decreased back-bonding from the iron atom to the bound CO. The lone pairs of the oxygen atoms of the hydroxyl groups prevent back-bonding by exertion of a strong negative electrostatic interaction. On the other hand, high nu(Fe-O(2)) frequencies are observed for the O(2) adducts of TCPs. In the resonance Raman (RR) spectrum of oxy-TCP-IM, we observed simultaneous enhancement of the Fe-O(2) and O-O stretching modes. Furthermore, direct evidence for hydrogen bonding between the hydroxyl groups and bound dioxygen was obtained by RR and IR spectroscopy. These spectroscopic data strongly suggest that O(2) and CO binding to TCPs is controlled mainly by the two different electrostatic effects exerted by the overhanging OH groups: destabilization of CO binding by decreasing back-bonding and stabilization of O(2) binding by hydrogen bonding.

Algorithms↗
PubMed2002

Histological examination of beta-tricalcium phosphate graft in human femur.

Prominent osteoconductive activity and the biodegradable nature of beta tricalcium phosphate (beta-TCP) for bone grafts in animal experiments has been reported. A new type of beta-TCP has been manufactured at extraordinarily high purity and has been available as potent bone grafting substitute for clinical use. The histological features of grafted beta-TCP in human bone have been analyzed. A 33-year-old female with a bone tumor of the proximal femur underwent curettage and beta-TCP graft under the diagnosis of probable benign fibrous dysplasia. Four weeks later, the proximal femur, including the grafted beta-TCP was resected because of the final diagnosis of the curettaged materials was osteosarcoma. The resected specimen revealed abundant direct new bone apposition on beta-TCP. There was no cartilaginous tissue or enchondral ossification. Bone formation was more prominent in the periphery of the grafted area than in the center. There was a considerable number of osteoclast-like giant cells surrounding the beta-TCP. This case illustrated that highly purified beta-TCP had prominent osteoconductive activity and biodegradable nature in human bone.

Absorbable Implants↗
PubMed1993

The effect of calcium phosphate ceramic composition and structure on in vitro behavior. II. Precipitation.

The formation of a biologically equivalent carbonate-containing apatite on the surface of synthetic calcium phosphate ceramics (CPC) may be an important step leading to bonding with bone. Reactions of several single phases CPCs upon immersion into a simulated physiologic solution (SPS) with an electrolyte composition of human plasma were determined. The CPCs covered a wide range of solution stabilities from low-soluble hydroxyapatites (HA) to metastable tricalcium phosphates (TCP) and tetracalcium phosphate (TTCP). Changes in chemical compositions of SPS and infrared spectral features after CPC immersion were analyzed. New phase formation was observed on all the CPCs. However, kinetics, compositions, and structures of the new phases were significantly different. The studied CPCs can be characterized by the time to new phase formation in vitro; the minimum time for measurable precipitate formation was found to increase in the order: not-well-crystallized HAs < well-crystallized HAs < alpha-TCP, TTCP < beta-TCP. Among the CPCs only not-well-crystallized HAs led to immediate new phase formation. The metastable CPCs, beta-TCP, alpha-TCP, and TTCP required an induction time during which dissolution occurred. beta-TCP showed the longest induction time and the lowest lattice ion uptake rate of all the CPCs tested. Only the not-well-crystallized HAs elicited immediate formation of carbonated HA. The well-crystallized HAs and beta-TCP did not elicit carbonated apatite formation within the time frame of the experiment. Instead, intermediate phases were formed. On alpha-TCP amorphous calcium phosphate (ACP) with a relatively low carbonate content was formed. TTCP was found to transform extensively to poorly crystallized carbonated apatite after 2 days of immersion.

Biocompatible Materials↗