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At least 667 records · Page 37Linked to original sources
PubMed1994

An electrophilic affinity ligand based on (+)-MK801 distinguishes PCP site 1 from PCP site 2.

The electrophilic affinity ligand, (+)-3-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycl ohepten-5,10 - imine hydrochloride [(+)-MK801-NCS] was characterized for its ability to acrylate phencyclidine (PCP) and sigma binding sites in vivo. Initial studies, conducted with mouse brain membranes, characterized the binding sites labeled by [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP). The Kd values of [3H]TCP for PCP site 1 (MK801-sensitive) and PCP site 2 (MK801-insensitive) were 12 nM and 68 nM, with Bmax values of 1442 and 734 fmol/mg protein, respectively. Mice were sacrificed 18-24 hours following intracerebroventricular administration of the acylator. The administration of (+)-MK801-NCS increased [3H]TCP binding to site 2, but not to site 1. Although (+)-MK801-NCS decreased [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d; ccyclohepten-5,10-imine maleate ([3H](+)-MK801) binding to site 1, it had no effect on [3H]TCP binding to site 1. Viewed collectively with other published data, these data support the hypothesis that PCP sites 1 and 2 are distinct binding sites, and that [3H]TCP and [3H](+)-MK801 label different domains of the PCP binding site associated with the NMDA receptor.

Affinity Labels↗
PubMed2005

Repair of sheep metatarsus defects by using tissue-engineering technique.

Tissue-engineering bone with porous ,betatricalcium phosphate (3-TCP) ceramic and autologous bone marrow mesenchymal stem cells (MSC) was constructed and the effect of this composite on healing of segmental bone defects was investigated. 10-15 ml bone marrow aspirates were harvested from the iliac crest of sheep, and enriched for MSC by density gradient centrifugation over a Percoll cushion (1. 073 g/ml). After cultured and proliferated, tissue-engineering bones were constructed with these,cellS seeded onto porous f-TCP, and then the constructs were implanted in 8 sheep left metatarsus defect (25 mm in length) as experimental group. Porous ,-TCP only were implanted to bridge same size and position defects in 8 sheep as control group, and 25 mm segmental bone defects of left metatarsus were left empty in 4 sheep as blank group. Sheep were sacrificed on the 6th, 12th, and 24th week postoperatively and the implants samples were examined by radiograph, histology, and biomechanical test. The 4 sheep in blank group were sacrificed on the 24th week postoperatively. The results showed that new bone tissues were observed either radiographic or histologically at the defects of experimental group as early as 6th week postoperatively, but not in control group, and osteoid tissue, woven bone and lamellar bone occurred earlier than in control group in which the bone defects were repaired in "creep substitution" way, because of the new bone formed in direct manner without progression through a cartilaginous intermediate. At the 24th week, radiographs and biomechanical test revealed an almost complete repair of the defect of experimental group, only partly in control group. The bone defects in blank group were non-healing at the 24th week. It was concluded that engineering bones constructed with porous -TCP and autologous MSC were capable of repairing segmental bone defects in sheep metatarsus beyond "creep substitution" way and making it healed earlier. Porous ,-TCP being constituted with autologous MSC may be a good option in healing critical segmental bone defects in clinical practice and provide insight for future clinical repair of segmental defect.

Animals↗
PubMed1998

Biodegradation of tricalcium phosphate ceramics by osteoclasts.

Biodegradation of tricalcium phosphate (TCP) ceramics was observed through mixed culture of osteoclasts and TCP discs in vitro in this study. Osteoclasts were isolated from newborn SD rat's marrow of long bone and cultured on TCP discs. The culture terminated at the 48th h and 96th h respectively. Under an inverted microscope, the osteoclasts imparted round or oval body with multinuclear and many thin processes. These cells were positively stained for tartrate-resistance acid phosphatase (TRAP). Scanning electron microscope showed that many resorption lacunae on TCP disc surface and their diameters were smaller than 20 microns. Osteoclasts were located in the lacunae. At the 96th h, the resorption lacunae become larger and osteoclasts showed degeneration. It is suggested that osteoclasts possess ability to re-absorb TCP ceramics under in vitro culturing condition.

Animals↗
PubMed2003

Quantitative evaluation of the biocompatible and osteogenic properties of a range of biphasic calcium phosphate (BCP) granules using primary cultures of human osteoblasts and monocytes.

A range of 50% porous gamma-sterilized biphasic calcium phosphate (BCP) granules, (20, 50, 80, and 100% tricalcium phosphate, TCP) were classified into two distinct size ranges, small 2-4 mm in diameter and large 4-6 mm in diameter, and their potential as bone graft extender materials was assessed in vitro using culture systems of primary-derived peripheral human blood monocytes and human osteoblasts isolated from bone. The effect of the in vitro culture conditions was evaluated prior to the introduction of the test substrates. The cellular response was assessed via quantification of viable cell adhesion to the materials, lactate dehydrogenase (LDH), the production and release of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2). The higher content TCP materials, 80% and 100% TCP, had a detrimental effect on viable cell adhesion after day 1, which was not related to calcium release from the granules within the local environment. TCP granules (20% and 50%) initiated a controlled level of inflammatory response that sustained and promoted viable macrophage adhesion throughout the test period, The percentage of TCP within the BCP granules was a governing factor in determining the cellular response.

Biocompatible Materials↗
PubMed2004

Dermal absorption of chlorpyrifos in human volunteers.

OBJECTIVE: The methods and results are described of a study on the dermal absorption of chlorpyrifos (CPF) in humans established via urinary excretion of the metabolite 3,5,6-trichloro-2-pyridinol (TCP). METHODS: Two dermal, single, doses of CPF were applied in two study groups (A and B) each comprising three apparently healthy male volunteers who gave their written informed consent. The clinical part of the study was conducted in compliance with the ICH Guideline and the EC principles of good clinical practice (GCP). An approximately 0.5 ml dilution of CPF in ethanol was applied to an area of approximately 100 cm(2) of the volar aspect of the forearm, resulting in doses of either 5 mg (A) or 15 mg (B) of CPF per study subject. Duration of dermal exposure was 4 h, after which the non-absorbed fraction was washed off. The following samples were collected at pre-determined intervals for the determination of either CPF or its metabolite TCP: dosing solutions, wash-off fractions and urine samples collected up to 120 h after dosing. RESULTS: A relatively large fraction of CPF (42%-67% of the applied dose) was washed off from the exposed skin area. Application of either 5 mg (A) or 15 mg CPF (B) resulted in the total urinary excretion of 131.8 microg (A) or 115.6 microg (B) of TCP 120 h after dosing. This indicated that 4.3% of the applied dose has been absorbed (A), while in group (B) no significant increase in urinary TCP (115.6 microg) was established. The latter indicates that an increase in the dermal dose at a fixed area does not increase absorption, which suggests that the percutaneous penetration rate was constant. Further, it was observed that the clearance of CPF by the body was not completed within 120 h, suggesting that CPF or TCP was retained by the skin and/or accumulated in the body. A mean elimination half-life of 41 h was established. CONCLUSION: The results show that daily occupational exposure to CPF may result in accumulation of CPF and/or its metabolites, possibly resulting in adverse effects.

Adult↗
PubMed2006

Tissue responses to an experimental calcium phosphate cement and mineral trioxide aggregate as materials for furcation perforation repair: a histological study in dogs.

The aim was to evaluate histologically the inflammatory reactions and tissue responses to an experimental tricalcium phosphate cement (TCP) and mineral trioxide aggregate (MTA) when used as repair materials in furcation perforations in dogs. Perforations were performed in 24 mandibular premolars of six anaesthetised dogs and filled either with ProRoot MTA (grey) or TCP. The root canals were subsequently shaped and filled, and the access cavities were closed with a bonded composite resin. The animals were killed at 12 weeks. After radiological examination, the teeth and surrounding structures were processed for light microscopy. Concerning the grades of inflammation, MTA exhibited significantly better results than TCP (chi-square test according to Pearson). No furcation was free of inflammatory cells. Mild inflammation was observed in nine of twelve cases with MTA and only twice in those with TCP. No significant differences were revealed between MTA and TCP in terms of bone reorganization or deposition of fibrous connective tissue (Mantel-Haenszel chi-square test). The grade of radiological examination corresponded with the grade of inflammation or differed by only one grade plus or minus. Perforations located in the furcation of teeth remain an endodontic and a periodontal problem with an uncertain prognosis, in spite of the promising modern materials applied.

Aluminum Compounds↗
PubMed2006

Observation and quantitative analysis of rat bone marrow stromal cells cultured in vitro on newly formed transparent beta-tricalcium phosphate.

To observe living cell morphology on ceramics by light microscopy, we fabricated a new material-transparent beta - tricalcium phosphate (t-beta TCP) ceramic-for the purpose of serving as a tissue culture substrate. Bone marrow stromal cells (BMSCs) were obtained from rat femora and cultured on both t-beta TCP ceramic disks and culture grade polystyrene (PS) dishes in an osteogenic medium. After 1 day of culture, cell attachment and spreading on both the t-beta TCP and PS substrata were equally and clearly detected by ordinary light microscopy. After 14 days of culture, extensive cell growth, alkaline phosphatase (ALP) staining, and bone mineral deposition could be detected on both substrata. In addition, quantitative biochemical analyses revealed high DNA content, ALP activity, and osteocalcin content of these cultures. This experiment is significant in that all of the results were similarly observed on both the t-beta TCP and PS substrata, indicating the excellent properties of beta TCP ceramics for BMSCs culture towards osteogenic differentiation.

Alkaline Phosphatase↗
PubMed2006

Bioactive ceramic composites sintered from hydroxyapatite and silica at 1,200 degrees C: preparation, microstructures and in vitro bone-like layer growth.

Bioceramic composites were synthesized by sintering the powders of hydroxyapatite (HAp) mixed directly with additive of 0.5, 1.0, 2.0, 5.0 and 10 wt.%SiO(2), respectively, at 1,200( composite function)C. X-ray diffraction (XRD) analysis indicated that the phase transformation from HAp to tricalcium phosphate (TCP) comprising alpha-TCP and Si-TCP occurred and became more prominent with the addition of SiO(2) and the increase in SiO(2) content. The observations of their surface microstructures showed that the addition of SiO(2) suppressed the grain growth and promoted the formation of crystalline-glassy composites denoted HAp + TCP/Bioglass. As the SiO(2) content is as high as 5 wt.%, the composite made a feature of crystalline clusters with different sizes consisting of HAp and TCP grains surrounded by the matrix of glassy phase. Furthermore, the dependence of in vitro bioactivity of these composites on the SiO(2) content was biomimetically assessed by determining the changes in surface morphology, i.e., bone-like apatite layer growth, after soaking in an acellular stimulated body fluid (SBF) for 3 days at 36.5( composite function)C. It was found that the HAp-SiO(2) composites showed a much faster bone-like layer growth than pure HAp, and the propensity of composites to exhibit a better bioactivity was getting more notable with increasing SiO(2) content, except for the case of the highest content of 10 wt.%. It was believed that the formation of the bone-like layer on the surfaces of these bio-composites is closely related to the increasingly provided silanol groups and transformed TCP phase in materials associated with the content of SiO(2) added.

Biocompatible Materials↗
PubMed1991

Pulpal response to tricalcium phosphate as a capping agent.

The purpose of this study was to evaluate tricalcium phosphate (TCP) as a pulp-capping agent. Two adult male beagle dogs were used for this investigation. Class I cavities were prepared in the posterior teeth and Class V cavities in the anterior teeth. With the use of a rubber dam and high speed with water coolant, minimal pulp exposures were created in both the experimental and control teeth, by means of a 1/2 round bur. Zinc oxide-eugenol was the temporary filling material used to restore all cavities. In each dog, five teeth served as control and were capped with the use of calcium hydroxide. In one dog, 10 teeth from two quadrants were capped with the tested material (TCP). In the other dog, 11 teeth were capped with TCP. Four teeth from the fourth quadrant in each dog were capped with a mixture of calcium hydroxide and TCP in a ratio of 1:1 by weight (50/50 group.) The two dogs were killed after 70 days. The histologic evaluation of the response to the capping agents and at the exposure site was recorded. A total of 39 teeth were evaluated in this study. It was found that TCP as a capping agent precipitated the highest mean inflammatory response and also demonstrated the highest percentage of reparative dentin formation.

Animals↗
PubMed1984

Chlorpyrifos: pharmacokinetics in human volunteers.

The kinetics of chlorpyrifos, an organophosphorothioate insecticide, and its principal metabolite, 3,5,6-trichloro-2-pyridinol (3,5,6-TCP), were investigated in six healthy male volunteers given a single 0.5 mg/kg po and, 2 or more weeks later, a 0.5 or 5.0 mg/kg dermal dose of chlorpyrifos. No signs or symptoms of toxicity or changes in erythrocyte cholinesterase were observed. Plasma cholinesterase was depressed to 15% of predose levels by the 0.5 mg/kg po dose but was essentially unchanged following the 5.0 mg/kg dermal dose. Blood chlorpyrifos concentrations were extremely low (less than 30 ng/ml), and no unchanged chlorpyrifos was found in the urine following either route of administration. Mean blood 3,5,6-TCP concentrations peaked at 0.93 micrograms/ml 6 hr after ingestion of the oral dose and at 0.063 micrograms/ml 24 hr after the 5.0 mg/kg dermal dose. 3,5,6-TCP was cleared from the blood and eliminated in the urine with a half-life of 27 hr following both the po and dermal doses. An average of 70% of the po dose but less than 3% of the dermal dose was excreted in the urine as 3,5,6-TCP; thus only a small fraction of the dermally applied chlorpyrifos was absorbed. Chlorpyrifos and its principal metabolite were rapidly eliminated and therefore have a low potential to accumulate in man on repeated exposures. Based on these data, blood and/or urinary 3,5,6-TCP concentrations could be used to quantify the amount of chlorpyrifos absorbed under actual use conditions.

Administration, Oral↗
PubMed1984

Vasoactive agonists prevent erythrocyte extravasation in thrombocytopenic hamsters.

The mediating action of selected vasoactive amines and their respective antagonists on vascular fragility, visible as cutaneous petechiae, was assayed with thrombocytopenic (TCP) hamsters. Serotonin (5-HT), norepinephrine (NE), epinephrine, dopamine and isoproterenol administered IP reduced petechiae significantly within 10 min; phenylephrine had no effect. Of the natural amines, 5-HT and NE were most effective in reducing petechial sensitivity to values obtained with untreated, normal animals; hence these two amines only were tested pharmacologically. Pretreatment of TCP animals with Ketanserin or propranolol, administered IP or IV, abolished any petechial inhibitory action of 5-HT and NE respectively; pretreatment with phenoxybenzamine reduced significantly the NE inhibition of petechiae, but to a lesser degree than propranolol. In contrast, atenolol, prazosin and yohimbine had no significant effect. Ketanserin abolished the action of NE, but adrenoceptor blockers had no effect on 5-HT-treated TCP hamsters. The results suggest that 5-HT and NE inhibition of petechiae may be receptor-mediated and that there may be receptor interaction. This was supported by the observation that non-additive subthreshold doses of 5-HT and NE, which individually did not prevent petechial formation in TCP hamsters, when combined totally inhibited petechiae. The theorized importance of endogenous 5-HT and NE to maintain postcapillary venule junctional integrity (site of petechial hemorrhaging) was also demonstrated by treating normal hamsters with drugs known to block or antagonize either 5-HT or NE uptake. In every instance petechial sensitivity rapidly occurred, and the loss of microvascular integrity in Ketanserin-treated hamsters mimicked quantitatively the petechial sensitivity observed with TCP animals.

Animals↗
PubMed1991

Adhesion and growth of cultured human endothelial cells on perfluorosulphonate: role of vitronectin and fibronectin in cell attachment.

The suitability of neutralized perfluorosulphonic acid (Nafion) as a surface for the attachment and growth of human cells was investigated in tissue culture. Nafion was equivalent to tissue culture polystyrene (TCP), and markedly better than polytetrafluoroethylene (Teflon), for the attachment and growth of human umbilical artery endothelial (HUAE) cells. The attachment and growth of HUAE cells on Fn-coated Nafion was equivalent to that on Fn-coated TCP. The contribution to the attachment and spreading of HUAE cells that is due to adsorption of serum fibronectin (Fn) or vitronectin (Vn) on to the Nafion or TCP was directly tested by selective removal of Fn or Vn from the serum before addition to the culture medium. HUAE cells seeded on to Nafion or TCP in medium depleted of Vn failed to attach and spread on to these surfaces, as measured after 4 or 24 h of culture. HUAE cells seeded in medium depleted of Fn, but containing Vn, attached and spread on to Nafion, albeit to a decreased extent as compared to that in intact serum when measured after 4 h of culture, and there was no effect of depletion of Fn when measured after 24 h of culture. HUAE cells seeded on to TCP in medium depleted of Fn became attached and spread during 4 h of culture. Our results show that Nafion is a suitable polymeric surface for the attachment and growth of human cells, including endothelial cells. For HUAE cells, adsorption on to the surface of an adhesive glycoprotein, such as Vn or Fn, is an essential step for attachment and spreading of the cells onto the Nafion surface.

Biocompatible Materials↗
PubMed1979

Tranylcypromine induced hypertension is not mediated by the inhibition of prostacyclin synthesis.

Tranylcypromine (TCP) is a monoamine oxidase inhibitor used extensively in the treatment of patients with reactive depression. Hypertensive crisis can complicate drug therapy, but the mechanism through which TCP causes high blood pressure is unknown. The present study was undertaken because recent investigations have shown that TCP can inhibit production of a potent vasodilator hormone, prostacyclin (PGI2), by blood vessels, possibly explaining the mechanism of pressor effects by the drug. Heart rate, left atrial, pulmonary artery and aortic pressures were monitored in dogs under control conditions and continuously following the IV infusion of TCP at the rate of 1 mg/kg over a period of one minute. Right femoral and the left internal mammary arteries were obtained during the control period and the left femoral and right internal mammary arteries resected between 6 and 30 minutes following drug infusion for PGI2 studies. Concentrations of the drug that caused significant elevation of the mean systemic pressure to 203 +/- 8 mmHg had no inhibitory effect on PGI2 production. Therefore, the influence of TCP on the hemodynamic parameters does not appear to be mediated through the inhibition of vascular PGI2 synthesis.

Animals↗
PubMed1994

Stress and/or tranylcypromine treatment affects serotonergic measures in blood and brain in rats.

Since stress can alter serotonin (5-hydroxytryptamine, 5-HT) turnover in the brain and the periphery, the effects of different types of acute stress on serotonin and related substances in the whole blood and various brain areas in rats pretreated with tranylcypromine (TCP) were studied. TCP administered alone caused a rise in 5-HT, a fall in its metabolite (5-hydroxyindoleacetic acid, 5-HIAA) in the whole blood and in every part of the brain analyzed relative to controls. In rats given TCP and subjected to footshock or water-immersion restraint stress similar changes, but to a different extent, were observed. 5-HT level remained essentially constant except in the blood and the limbic system, whereas 5-HIAA level was found to be increased in the blood and the brain, mainly in the limbic system and the brainstem following footshock. Water-immersion restraint stress caused an increase in 5-HT only in the limbic system without any changes in 5-HT and 5-HIAA in the blood. Relative to controls, an increase in total tryptophan concentration in the whole blood and in every part of the brain was found only after footshock application with or without pretreatment with TCP. In conclusion, responses to stress in rats may depend upon the type of stimulus applied as well as of a concurrent administration of TCP. Some regional differences may account for an altered in vivo efficacy of this drug.

Animals↗
PubMed1989

Significance of toxin-coregulated pili as protective antigens of Vibrio cholerae in the infant mouse model.

The infant mouse cholera model has been used to evaluate the relative importance of toxin-coregulated pili (TCP) as protective antigens of Vibrio cholerae 01. Electron microscopic and immunoblotting analyses revealed that, under the cultural conditions examined, TCP were only expressed by strains of classical biotype. Antibodies to TCP were sufficient to confer protection against two such strains, and were more efficient if the challenge vibrios were cultured for TCP expression. In contrast, such antibodies did not protect mice against challenge with any of four strains of El Tor biotype. Since two of the latter have previously been shown to possess non-lipopolysaccharide protective antigens, these results suggest that TCP are not the only such antigen in this model.

Animals↗
PubMed1996

Determination of tris(4-chlorophenyl)methanol and tris(4-chlorophenyl)methane in fish, marine mammals and sediment.

Tris(4-chlorophenyl)methanol (TCP) and tris(4-chlorophenyl)methane (TCPMe) were determined in aquatic organisms and sediment by a method based on Soxhlet extraction, gel permeation chromatography, fractionation over silica and gas chromatography/mass spectrometry (GC/MS) analysis. TCPMe was identified as the 4-substituted isomer after synthesis of this compound. TCP could be determined by GC/MS with negative chemical ionistation (GC/NCI-MS) with a detection limit of 0.02 g kg(-1) and a recovery of 90%. TCP concentrations in marine mammals from the North Sea and Dutch Wadden Sea ranged from 0.2 to 2 mg kg(-1), and those in marine and freshwater fish samples from 0.005 to 0.4 mg kg(-1) on a lipid wt basis. TCP concentrations in two Rhine delta sediment samples were 1.2 and 3.0 microg kg(-1) dry wt, respectively. TCPMe concentrations, determined by GC/MS with electron impact (GC/EI-MS), were 10-50% of the TCP concentration in all samples analysed.

Journal Article↗
PubMed1986

Evaluation of the reproductive toxicology of 2,4,6-trichlorophenol in male and female rats.

The toxicity of chlorinated organic compounds which may be generated as a by-product of drinking water chlorination has been an issue of increasing concern. Relatively few data are available concerning their reproductive toxicity. The present study was designed to evaluate the reproductive effects of one of these compounds, 2,4,6-trichlorophenol (TCP), in male and female rats. Adult males were treated with either 0, 100, 500, or 1000 mg/kg of TCP (po) for 10 weeks, at which time semen evaluations were conducted on ejaculates recovered from the genital tract of receptive females. Fertility was assessed in the 0- and 1000-mg/kg groups. Females were treated with identical doses for 2 weeks prior to pregnancy then throughout gestation. Dams were allowed to litter and pup development was monitored until Day 42 postpartum. TCP had no effect on any sperm parameter or male fertility. Treatment of females with 1000 mg/kg of TCP produced gross maternal toxicity as reflected in increased lethality and decreased weight gains in the dams. However, no treatment-related differences were seen in litter sizes or pup survival. Male and female birth weights were significantly depressed in the 500- and 1000-mg/kg groups; these differences disappeared by Day 4 postpartum, suggesting that they were a reflection of maternal toxicity. To this extent, the reproductive processes of male and female rats do not appear to be a primary target for the effects of TCP.

Animals↗
PubMed1988

Reproductive toxicity of tricresyl phosphate in a continuous breeding protocol in Swiss (CD-1) mice.

The effects of a mixture of tricresyl phosphate isomers on reproductive performance in Swiss (CD-1) mice were evaluated using a continuous breeding protocol. Tricresyl phosphate (TCP) was mixed into the feed at 0, 0.05, 0.1, and 0.2% by weight. Although the fertility index was not changed in the animals consuming the high-concentration feed, the number of litters per pair decreased in a dose-related fashion, and the proportion of pups born alive, and their weight, was significantly decreased in the high-dose group. A crossover mating trial found impaired fertility in both males and females exposed to 0.2% TCP, with a greater effect in females. Histopathology of the F0 pairs revealed dose-related seminiferous tubule atrophy, and decreased testis and epididymal weights in the high-dose males, while the female reproductive tract showed no histopathologic changes. There were dose-related changes in the adrenals of both sexes, and body weight was depressed in both sexes at the highest concentration. The last litter born in the 98-day breeding phase was reared to age 74 days and then mated within the control and two of the treatment groups (0.0, 0.05, and 0.1% TCP; there were too few offspring in the 0.2% group). There was a decrease in the fertility index in the 0.1% TCP group, and a decreased proportion of liveborn and number of liveborn pups per litter. In the F1 males at necropsy, sperm concentration and morphology were normal at termination, although motility was decreased in both the 0.05% and the 0.1% groups compared to controls. These data show that TCP impaired fertility in both sexes of mice in the F0 generation and affected sperm motility at even the lowest dose in F1 males.

Adrenal Glands↗