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PubMed1999

Neuronal differentiation in PC12 cells is inhibited by chlorpyrifos and its metabolites: is acetylcholinesterase inhibition the site of action?

Developmental expression of AChE has been associated with neuronal differentiation (P. G. Layer and E. Willbold, Prog. Histochem. Cytochem. 29, 1-94, 1995). In this study we used pheochromocytoma (PC12) cells, a noncholinergic cell line, rich in acetylcholinesterase (AChE) activity, to examine the effects of cholinesterase-inhibiting pesticides on neural differentiation. The experimental paradigm was focused on whether alterations in cholinesterase (ChE) activity by a pesticide or its metabolites would affect neurite outgrowth, a morphological marker of neuronal differentiation. Results indicated that (1) in controls, both total ChE and AChE activities were significantly increased in NGF-primed PC12 cells compared to NGF-unprimed cells, while the basal expression of butyrylcholinesterase (BuChE) activity was much lower (1.3-7% of total ChE activity) in either the presence or the absence of NGF; (2) an increase in AChE activity was highly correlated (r(2) = 0.99) with the extension of neurite outgrowth, suggesting a link between the expression of AChE activity and the elaboration of neurite outgrowth; (3) NGF increased neurite outgrowth in a time- and concentration-dependent manner; and (4) either chlorpyrifos (CPF) or its metabolites (CPF oxon and TCP) inhibited NGF-induced neurite outgrowth (branches per cell, fragments per cell, total neurite outgrowth per cell) in PC12 cells. These data suggest that the expression of AChE activity is associated with the extension of neurite outgrowth. Both enzyme activity and neurite branching were disrupted by CPF oxon; however, CPF and its other metabolite TCP (1 microgram/ml) caused inhibition of neurite outgrowth in the absence of ChE inhibition, suggesting an alternative mechanism(s) may be involved in pesticide-induced inhibition of differentiation.

Acetylcholinesterase↗
PubMed1987

Rats and marmosets respond differently to serotonin agonists and antagonists.

The actions of the serotonin precursor 5-hydroxytryptophan (5-HTP), the agonist 5-methoxy-N,N-dimetyltryptamine (MeODMT) and quipazine (QPZ) and the antagonists cyproheptadine, methysergide and metergoline, were studied in the rat and in the common marmoset (Callithrix jacchus). The precursor and agonists elicited head shakes, forepaw padding, splayed hindlimbs, tremor and Straub tail in the rat. However, head shakes were not observed after MeODMT and Straub tail was not observed after QPZ. Carbidopa plus 5-HTP potentiated only head shakes, while tranylcypromine (TCP) plus 5-HTP potentiated all the behaviors above. In the marmoset, the action of these drugs elicited drowsiness, teeth chattering, ataxia, vomiting and decreased motor activity, although vomiting was not elicited by MeODMT and ataxia and drowsiness by QPZ. Although TCP plus 5-HTP potentiated all these behaviors, carbidopa plus 5-HTP was not effective. Rats treated with the antagonists (1.0, 5.0 and 10 mg/kg doses) did not show any of these behaviors, but marmosets treated with the same drugs developed "drowsiness", vomiting, and decreased motor activity; nonetheless, cyproheptadine (5.0 and 10 mg/kg doses) did not elicit "drowsiness", while increasing motor activity and the number of head shakes. Pretreatment of marmosets with these antagonists blocked only teeth chattering elicited by MeODMT (4.0 mg/kg) and QPZ (10 mg/kg). Pretreatment with haloperidol, p-chlorophenylalanine and alpha-methyl-P-tyrosine had no effect. The data obtained show that rats and marmosets present differential behavioral responses to the 5-HT drugs used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Extent of the mouse t complex and its inversions shown by in situ hybridization.

Probes for loci situated near one end of the proximal (Tcp-1) and distal (Qa-2, 3) inversions of the mouse t complex have been hybridized to chromosomes of mice with and without t complexes and with morphologically distinguishable chromosome 17s. Both the probe for Tcp-1 and that for Qa-2, 3 hybridized to clearly different positions on t and non-t chromosomes, thus making visible the extent of the two inversions. The proximal inversion extends from roughly the junction of bands A1 and A2 to band A3, and the distal inversion from band A3 to band C. Thus, the whole t complex extends from the band A1-A2 junction to band C, and is therefore somewhat larger than previously thought, and occupies about 1.2% of the genome. A probe for complement component 3 (C3-1), genetically known to be several cM distal to the t complex, was found by in situ hybridization to lie in band E1. The proximal part of chromosome 17 is one of the best known parts of the mouse genome, at both the genetic and molecular levels. It may soon be possible to correlate the length of the t complex in terms of chromosomal distance with its physical length in megabases.

Animals↗
PubMed1977

Changes in the ultrastructure of satellite cells of slow loris in tricresylphosphate poisoning.

Toxic reaction of satellite cells from posterior root ganglia of slow loris in TCP poisoning is described. The satellite cells in experimental animals show a marked increase in the rough ER, Golgi complex, microvesicles and filaments. Furthermore there is also an increase in the number of dense bodies and mitochondrial density in these cells. The significance of these changes are discussed and it is concluded that in TCP poisoning not only the neurons but the supporting cells are also affected.

Animals↗
PubMed1993

Phencyclidine treatment in mice: effects on phencyclidine binding sites and glutamate uptake in cerebral cortex preparations.

The effects of a psychotomimetic drug, phencyclidine (PCP), on glutamatergic neurotransmission were studied in mice. The binding of tritiated N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) to cerebral cortical membranes and the uptake of [3H]glutamate by cortical synaptosomal preparations were assessed after PCP treatment (1 mg/d/mouse for 3 days) with implanted minipumps. The binding capacity Bmax of TCP significantly increased but the binding constant KD remained the same after PCP exposure, indicating that more binding sites became available. The basic properties of the binding remained unaltered but the actions of glutamate, glutamate receptor agonists and glycine were potentiated in PCP-treated mice. The uptake of glutamate was saturable, consisting of both high- and low-affinity transport components. After PCP exposure the transport constant Km of the high-affinity component increased and that of the low-affinity component was not changed. The maximal velocity V of the high-affinity component increased while that of the low-affinity transport decreased. Moreover, inhibition by structural analogues was potentiated, suggesting modification of the glutamate transporter. The results show that chronic PCP treatment, used as a model of psychosis, markedly affects the studied glutamatergic parameters.

Animals↗
PubMed1983

[Release delay of various antibiotics from resorbable tricalcium phosphate ceramic granules with soluble coating for local treatment of osteomyelitis. An animal experiment study].

The releasing kinetic of antibiotics from tricalcium phosphate beads was studied in animal experiments. The porous TCP-beads were filled with antibiotics and coated with biodegradable substances for delaying the release of the antibiotics. There were high tissue levels of antibiotics in the surrounding bone for many days. This method gains an increase in therapeutic safety in treatment of osteomyelitis. The coated TCP-antibiotic beads are used simultaneously as bone graft and for treatment of the bone infection. There is no need for further operation.

Animals↗
PubMed1989

Lithium alters the stereoselectivity of monoamine oxidase in rat brain.

The effects of lithium on monoamine oxidase (MAO) in rat brain were studied in the presence of each enantiomer of tranylcypromine [(+)- and (-)-TCP]. The (+)-enantiomer was 25 times more potent than its antipode as MAO inhibitor. Lithium enhanced the inhibitory effect of (-)-TCP on MAO, but it did not affect actions of the (+)-enantiomer. Moreover, lithium influenced the stereoselective index for MAO, which suggests that lithium altered conformational features of the enzyme.

Animals↗
PubMed1993

Acute biochemical variations induced by four different calcium salts in healthy male volunteers.

Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D3 supplements, may reduce non-vertebral fracture rates in elderly women. However, for many formulated pharmaceutical products their relative beneficial effects have not been conclusively established. We have compared the acute (6 h) metabolic responses following oral administration of two preparations of calcium gluconolactate and carbonate (CG and CG'), tricalcium phosphate (TCP) and calcium citrate (CC), given on separate occasions in each of 10 healthy young male volunteers. The subjects fasted overnight for 12 h and continued to fast during the experimental procedure. A 1000 mg dose of each Ca salt was ingested at weekly intervals. Blood was drawn after 30, 60, 90, 120, 180, 240, 300 and 360 min for measurement of serum Ca, phosphorus (P), parathyroid hormone (PTH) and whole plasma calcitonin (iCT). All Ca supplements induced significant (+6.4% to +8.1%; p < 0.01) increases in Ca and significant suppression of PTH (-37.4% to -57.4%; p < 0.01). Comparison of response curves revealed significantly (p < 0.01) more marked Ca increase and PTH suppression with CC than with the other three Ca salts. CG' and CC induced marginal decreases in serum P and the overall curve of P variations was different for TCP compared with CG, CG' and CC. No significant variation of iCT was recorded during the test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1978

A thermodynamic analysis of the secondary transition in the spontaneous precipitation of calcium phosphate.

A thermodynamic analysis has been made of the secondary transition stage in the spontaneous precipitation of calcium phosphate following the amorphous-crystalline transformation. The first formed crystalline material has a solubility similar to that of octacalcium phosphate (OCP) and the computed thermodynamic solubility product remains invariant in the pH range 7.00--8.60. The duration of the secondary stage is sensitive to pH and the transition appears to occur by hydrolysis of the first formed OCP-like phase to a more basic apatitic phase with a tricalcium phosphate (TCP) stoichiometry. The crystalline material at the end of this transition has an invariant solubility product, in the pH range 7.00 to 8.60, when the TCP-like molecular formula is assumed. Changes in the solution chemistry which accompany the solid-to-solid transitions are consistent with the above conclusions. The results of this study are also consistent with those of a previous study which suggest that the stability of the amorphous calcium phosphate phase is dependent upon the instability of the solution phase with respect to OCP formation.

Calcium↗
PubMed1991

Effects of sigma receptor ligands on schedule-controlled behavior of rats: relation to sigma and PCP receptor binding affinity.

Eleven drugs were examined for their ability to inhibit sigma and phencyclidine (PCP) receptor binding, as labelled by (+)[3H]-R-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), [3H]ditolylguanidine (DTG), (+)[3H]N-allylnormetazocine (NANM) and [3H]1-(1-(2-thienyl)cyclohexyl)piperidine (TCP), in membrane preparations from whole rat brain. The same drugs were studied for their effects under a fixed-ratio (FR) schedule of food reinforcement in rats. The relative potency order of the drugs for decreasing FR responding was: haloperidol greater than (+)-3-PPP greater than (-)NANM greater than BMY 14802 greater than PCP greater than (+)NANM greater than DTG greater than rimcazole greater than JO 1783 greater than JO1784 greater than (-)butaclamol. The binding affinities of all 11 drugs for either the [3H]DTG, (+)[3H]-3-PPP, (+)[3H]NANM or [3H]TCP site did not correlate significantly with the potencies of the same drugs for decreasing FR behavior. Rimcazole, (+)-3-PPP and haloperidol, at behaviorally inactive doses, were studied for their effects as antagonists of the rate-decreasing effects of JO 1784, DTG and (+)NANM: rimcazole attenuated the effects of DTG and (+)NANM but not JO 1784; (+)-3-PPP attenuated the effects of (+)NANM but not JO 1784 and DTG; and haloperidol was devoid of antagonistic actions. Moreover, BMY 14802 did not attenuate the rate-decreasing effects of (+)-3-PPP. These results further indicate that it is difficult to distinguish between purported sigma agonist and antagonist drugs.

Animals↗
PubMed1995

Optimisation of transcutaneous cardiac pacing by three-dimensional finite element modelling of the human thorax.

The goal of the study is to determine by finite element analysis (FE) the optimal electrode placement, size and electrolyte resistivity that minimise the pain experienced by patients during successful transcutaneous cardiac pacing (TCP). The three-dimensional FE model generated for this purpose has 55,388 nodes, 50,913 hexahedral elements and simulated 16 different organs and tissues, as well as the properties of the electrolyte. The model uses a non-uniform mesh with an average spatial resolution of 0.8 cm in all three dimensions. To validate this model, the voltage across 3 cm2 Ag-AgCl electrodes is measured when currents of 5 mA at 50 kHz are injected into a subject's thorax through the same electrodes. For the same electrode placements and sizes and the same injected current, the FE analysis produced results in good agreement with the experimental data. The optimisation analysis tested seven different electrode placements, five different electrode sizes and six different electrolyte resistivities. The analysis indicates that the anterior-posterior electrode placement, electrode sizes of about 90 cm2 and electrolytes with resistivity of about 800 omega.cm yield the most uniform current distribution through the skin, thus having the best chances to minimise the pain delivered to the patient during successful TCP. The anterior-anterior electrode placement is the second most efficient.

Cardiac Pacing, Artificial↗
PubMed1991

Thermal decomposition of Lingula shell apatite.

Lingula shell is composed of apatite with a preferred orientation. The shell apatites of Lingula unguis(Lu) and Lingula shantoungensis(Ls) were characterized and compared with apatite of human tooth enamel. Insight into the Lingula apatite was studied by following the change of lattice parameter, transformation to beta-tricalcium phosphate (beta-TCP), and the loss and change of CO3, OH, and H2O after heating up to 1,000 degrees C in air and N2 for 24 hours. The OH stretching band was not observed in unheated apatites and in apatites heated in dried N2. Lu and Ls apatite produced 26 and 17 wt% of beta-TCP at 700 degrees C, respectively. Fifty to 60% of H2O was lost at 200 degrees C, being accompanied by a drastic contraction of the a- and c-axis and a drastic decrease in the crystallinity. These results indicate that (1) Lu and Ls shell apatite is CO3 containing F + Cl-apatite, and (2) the structural H2O of the Lingula apatite is loosely bounded such that they are lost at lower temperature than tooth enamel.

Animals↗
PubMedDate not supplied

Effects of thioacetamide-induced hepatic failure on the N-methyl-D-aspartate receptor complex in the rat cerebral cortex, striatum, and hippocampus. Binding of different ligands and expression of receptor subunit mRNAs.

Hepatic encephalopathy (HE) is characterized by symptoms pointing at disturbances in glutamatergic neurotransmission in the brain, particularly in the striatum. The binding parameters of ligands specific for different recognition sites in the N-methyl-D-aspartate (NMDA) receptor complex and the distribution of the receptor subunit mRNAs (NR1, NR2A-D) were assessed in rats with acute HE induced with a hepatotoxin, thioacetamide (TAA). The binding of: 1. L-[3H]glutamate (NMDA-displaceable); 2. [3H]dizocilpine and N-(1-[2-thienyl]-cyclohexyl) [3H]piperidine ([3H]TCP); and 3. The coactivator site agonist [3H]glycine was assayed in purified membranes of the cerebral cortex, hippocampus, and striatum. In HE rats, Bmax of NMDA-displaceable glutamate binding was increased in the cerebral cortex and hippocampus, but slightly decreased in the striatum. In this region, the binding affinity was also slightly increased. In HE, Bmax of [3H]dizocilpine binding was unchanged in the striatum and cerebral cortex, but substantially decreased in the hippocampus. Pretreatment with phorbol ester enhanced the binding of dizocilpine more in HE than in control rats. Bmax of [3H]TCP binding was decreased in the cerebral cortex and striatum, but increased in the hippocampus. The different responses of these two phencyclidine site antagonists to HE may be indicative of a conformational change within the ion channel and/or the presence of microdomains reacting differently to extrinsic factors. HE did not affect glycine binding, but potentiated the maximal stimulation of [3H]dizocilpine binding by glycine in the cerebral cortex. The results emphasize the brain region and domain specificity of the responses of the NMDA receptor complex to HE.

Animals↗
PubMed1997

Reconstruction of calvarial defects by bioresorbable ceramics: an experimental study in rats.

This study evaluated bioresorbable ceramics in the reconstruction of calvarial defects. Full-thickness defects were made in the calvaria of 40 adult Sprague-Dawley rats (350-450 g) with a standard 8-mm trephine drill. Three different materials were used for defect repair: (a) pure alpha-tricalcium phosphate (TCP), (b) surface-treated glass ceramic, (c) surface-treated glass ceramic plus 70/30 L/DL polylactic acid (volume ratio 45/55). The implants were pellets of 7.9 mm diameter and 2 mm thickness and were inserted press fit into the calvarial defects. Each of these materials was inserted into ten animals. Five animals were evaluated each after 6 weeks and 26 weeks. For each interval there was a control group of five animals. After 6 weeks the control defects exhibited negligible bone regeneration at the defect margins but showed substantially more bone regeneration after 26 weeks extending up to 2.5 mm into the defect space. The TCP specimens showed a number of multinuclear cells on the material surface and direct bone/implant contact in a few locations but no signs of gross degradation or volume reduction after 6 weeks. The amount of bone ingrowth and cellular behavior had not changed after 26 weeks with resorption still going on. Glass ceramic implants by contrast appeared to be even better tolerated after 6 weeks with remarkable bone ingrowth and broad osseous fixation of the pellet to the defect margins and beyond, while highly vascular connective tissue filled the remaining pores of the implant. After 26 weeks the material had been extensively degraded, leaving behind only a few remnants, which were surrounded by seams of highly vascularized and cell-rich resorptive connective tissue with newly formed bone tissue nearly bridging the defect. The polylactic acid/ceramic composite implants showed hardly any tissue ingrowth or degradation either after 6 or after 26 weeks. Hence all tested materials appeared to be well tolerated at the site of implantation. However, gradual replacement by bone ingrowth tended to occur only in implants without polylactic acid.

Animals↗
PubMed1999

Ultrastructural study of apatite precipitation in implanted calcium phosphate ceramic: influence of the implantation site.

Macroporous biphasic calcium phosphate (MBCP) blocks were implanted into rabbit trabecular bone and muscle, recovered 18 weeks later, and then observed and analyzed by transmission electron microscopy (TEM), electron diffraction, and electron microprobes. The results showed that (1) apatitic microcrystals appeared by secondary nucleation in both bone and muscle sites; (2) precipitated microcrystals were aggregated around ceramic crystals in bone sites but distributed randomly and without orientation in micropores in muscle sites; (3) the ratio of calcium to phosphorus was higher for microcrystals in bone than muscle sites; and (4) precipitated microcrystals around beta-tricalcium phosphate (beta-TCP) crystals were less aggregated and dense than those around hydroxyapatite (HA). These findings suggest that microenvironmental parameters such as fluid circulation and the interaction of ceramics with proteins or cells affect the physicochemical dissolution/reprecipitation process. Epitaxic growth of apatitic microcrystals seems more favorable from HA than beta-TCP.

Animals↗
PubMed2003

Pharmacokinetics of long-term sufentanil infusion for sedation in ICU patients.

OBJECTIVE: To determine the pharmacokinetics of long-term infusion of sufentanil in ICU patients. DESIGN AND SETTING: Open-label study in a surgical intensive care unit. PATIENTS: Ten consecutive patients without renal or hepatic failure requiring mechanical ventilation for at least 6 days. INTERVENTIONS: Patients received sufentanil (initial bolus 0.5 micro g/kg and continuous infusion rate of 0.5 micro g/kg per hour) and midazolam (initial bolus 0.08 mg/kg and continuous infusion 0.05 mg/kg per hour). Sedation was adjusted according to the Ramsay scale (score >3). Blood samples were taken during and up to 72 h after the infusion, and plasma concentrations were measured using a sensitive radioimmunoassay method. MEASUREMENTS AND RESULTS: Plasma concentration-time profiles of sufentanil and pharmacokinetic parameters such as initial postinfusion half-life (t(1/2alpha)), elimination half-life (t(1/2beta)), total clearance (Cl), volume of distribution (Vdbeta), and time required to obtain a 50% decrease in plasma concentration (tcp(0/2)). The mean duration of sedation was 12+/-7 days. The initial half-life t(1/2alpha) was 1.33+/-1.15 h. The observed prolonged elimination half-life (t(1/2beta)=25.5+/-9.4 h) was related to the large volume of distribution (Vdbeta=22.6+/-9.4 l/kg). The mean total clearance was 13.4+/-7.0 ml/kg per minute. The mean time required to obtain a 50% decrease in plasma concentration was short (tcp(0/2=)4.7+/-3.7 h). CONCLUSIONS: The pharmacokinetic analysis of sufentanil for ICU sedation revealed increased volume of distribution and elimination half-life. Nevertheless the rapid distribution and elimination processes suggest that the rapid reversibility of sedation with sufentanil is maintained after long duration of infusion. Further studies should be carried out to evaluate the clinical relevance of these results.

APACHE↗
PubMed1998

The role of striatal dopaminergic mechanisms in rotational behavior induced by phencyclidine and phencyclidine-like drugs.

Phencyclidine (PCP) and phencyclidine-like drugs (TCP, dexoxadrol, MK-801, and SKF 10,047) were evaluated for their ability to induce rotational behavior in rats with unilateral 6-OHDA lesions of the medial forebrain bundle and for their ability to alter striatal dopamine (DA) overflow with microdialysis procedures. All of the compounds tested produced rotational behavior ipsilateral to the lesion, suggesting that they were enhancing extracellular dopamine in the intact striatum. The microdialysis studies, however, did not support this contention. There appeared to be a complete dissociation between the ability of the five compounds to produce ipsilateral rotations and their ability to enhance extracellular dopamine levels in the striatum. PCP was the only compound able to elicit significant increases in striatal dopamine overflow following i.p. injections and also produce dramatic rotational behavior. MK-801 was the most potent compound in enhancing rotational output while it had no effect at all on striatal dopamine overflow. Dexoxadrol also produced significant rotational output without having any effect on extracellular levels of dopamine following i.p. injections. TCP and SKF 10,047, at doses which produced significant rotational behavior, only elevated dopamine 16% and 12%, respectively, at peak effect. It is most parsimonious to conclude that the effects of PCP-like drugs on nigro-striatal function are mediated through their ability to act as indirect NMDA receptor antagonists and not through their ability to alter striatal dopamine activity.

Animals↗
PubMed2002

Simple and rapid determination of iodide in table salt by stripping potentiometry at a carbon-paste electrode.

A simple and rapid procedure, utilising constant-current stripping analysis (CCSA) at a carbon-paste electrode containing tricresyl phosphate as a pasting liquid (TCP-CPE), has been developed for the determination of iodide in table salt. Because of a synergistic accumulation mechanism based on ion-pairing and extraction of iodide in combination with electrolytic pretreatment of the TCP-CPE, the method is selective for iodide and enables direct determination of iodide in samples of table salt containing anti-caking agents such as K(4)[Fe(CN)(6)] (food additive "E 536") or MgO. The iodide content (calculated as KI) can be determined in a concentration range of 2 to 100 mg kg(-1) salt, with a detection limit (S/N=3) of 1 mg kg(-1), and a recovery from 90 to 115%. The proposed method has been used to determine iodide in several types of artificially iodised table salt and in one sample of natural sea salt. The results obtained agreed well with those obtained by use of three independent reference methods (titration, spectrophotometry, and ICP-MS) used to validate the CCSA method, indicating that the developed method is applicable as a routine procedure for rapid testing in salt production process control and in the analysis of marketed table salts.

Carbon↗