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Environmental residues and biomonitoring estimates of human insecticide exposure from treated residential turf.

Intentional and unavoidable human exposure is a consequence of using pesticides to nurture and protect residential turf. Limited exposure studies have been conducted for assessing potential human exposure of turf residues. Exposure was measured in persons who performed a 20-minute structured activity (Jazzercise) on chlorpyrifos (CP)-treated Kentucky bluegrass (12 +/- 4 microg CP/cm(2)). CP exposure was measured by determining urine clearance of the 3,5,6-trichloro-2-pyridinol (TCP). Study participants wore either 100% cotton whole body dosimeters (union suit, gloves, and socks) or exercise suits (shorts and a sports top or one-piece suit with similar amounts of exposed skin). An average of 1.6 mg CP/person was extracted from whole body dosimeters worn by study participants. The measured residue transfer was well below the 35 mg CP/person estimated using the US EPA standard operating procedures. Biomonitoring based on urine clearance of TCP indicated that an average of 1.3 microg CP/kg was absorbed. Absorbed dosages (0.5 to 2 microg CP/kg) derived from transferable residue on cotton cloths pressed to the turf with a weighted roller were similar to estimates from biomonitoring. A very limited amount of CP applied to turf is available for transfer and absorption during intensive human contact.

Absorption↗

Use of purified beta-tricalcium phosphate for filling defects after curettage of benign bone tumours.

Fifty-three patients with benign bone tumours were treated with curettage and filling with a purified beta-tricalcium phosphate (beta-TCP). Recurrences occurred in two cases. There was neither a postoperative infection nor adverse reaction due to the material. Postoperative fractures did not occur in any patients. Radiographically, complete resorption of the material and bone remodelling were achieved in 23 cases (43%). Of these 23 cases, there was a statistical correlation between the filling volume and the time taken for complete resorption (p<0.05). We concluded that purified beta-TCP was an ideal bone graft substitute for the treatment of benign bone tumours because of its good biocompatibility and resorption characteristics.

Adolescent↗

Degradation of chlorophenols using pentachlorophenol-degrading bacteria Sphingomonas chlorophenolica in a batch reactor.

Chlorophenols are common environmental contaminants that have been used as the major component in wide-spectrum biocides in industry and agriculture. Many chlorophenols tend to persist in the environment and may become public health hazards. This research studied the ability of the pentachlorophenol (PCP)-degrading bacterium Sphingomonas chlorophenolica to degrade and dechlorinate other chlorophenols. In addition, the characteristics of S. chlorophenolica were also investigated. When S. chlorophenolica cells were preincubated with PCP, the lag phase PCP degradation periods became shorter and the PCP concentrations that could be removed became higher. S. chlorophenolica was able to completely degrade 2,3,6-trichlorophenol (2,3,6-TCP), 2,4,6-trichlorophenol (2,4,6-TCP), 2,3,4,6-tetrachlorophenol (2,3,4,6-TeCP), and PCP within 38.1, 15.1, 11.8, and 11.8 h, and to release concentrations of 50.1, 60.9, 63.7, and 58.5 mg/L chloride at the same period of time. In the presence of supplementary carbon sources, the PCP removal efficiency increased with the presence of glucose or pyruvate. However, the removal efficiency of 75 mg/L 2,4-dichlorophenol did not increase with supplemental carbon sources.

Biodegradation, Environmental↗

Immunohistochemical analysis of protein expression after middle cerebral artery occlusion in mice.

The effect of transient focal cerebral ischemia on protein regulation was studied in mice using multiparametric immunohistochemistry. Injury was characterized by measurements of blood flow, regional protein synthesis and terminal transferase biotinylated-dUTP nick end labeling (TUNEL). The proteins studied were selected from a previously established list of differentially regulated proteins and included the GTPases dynamin, RhoB, CAS and Ran BP-1, the transcription factors Nurr1 and p-Stat 6, the protein kinase MAPK p49, the splicing factors SRPK1 and hPrp16, the cell cycle control proteins cyclin B1 and Nek2, the inflammatory proteins FKBP12 and Rag2, the cell adhesion protein paxillin and the folding protein TCP-1. Regulation patterns were diverse and comprised ipsi- and/or contralateral up- and down-regulation with or without topical association to impeding cell death. Some proteins (SRPK1, TCP-1 and Nurr1) also exhibited post-ischemic translocation from the nucleus to the cytosol. Our observations stress the importance of regional analysis for the interpretation of proteomic data, and contribute to the identification of new pathways that may be involved in the evolution of post-ischemic brain injury.

Animals↗

Potential of an ultraporous beta-tricalcium phosphate synthetic cancellous bone void filler and bone marrow aspirate composite graft.

Autogenous cancellous bone is considered to be the best bone grafting material. Autogenous bone grafts provide scaffolding for osteoconduction, growth factors for osteoinduction, and progenitor stem cells for osteogenesis. However, the procurement morbidity, limited availability, and expense associated with the use of autogenous bone grafts are significant disadvantages. Allografts and xenografts lack the osteoinduction and osteogenesis properties of autogenous bone, and they introduce the potential for both transferring disease and triggering a host immune response. Synthetic bone grafts [hydroxyapatite or tricalcium phosphate (TCP)], while good platforms for osteoconduction, lack any intrinsic properties of osteoinduction and osteogenesis. A composite graft that combines synthetic scaffold with autogenous osteoprogenitor cells from bone marrow aspirate (BMA), a low-morbidity procedure, could potentially deliver the advantages of autogenous bone grafts without the disadvantages. A new ultraporous beta-TCP construct, engineered using solution-derived nano-particle technology, may prove to be an ideal carrier for BMA in such a composite. The unique, interconnected macroporosity, mesoporosity, and microporosity of this synthetic cancellous bone void filler allows it to wick in cells and nutrients via enhanced capillarity. Preliminary canine data support this expectation, demonstrating bone formation that suggests good penetration of cells and nutrients. These results suggest that BMA cells, absorbed into such a scaffold, may remain viable, thereby potentially making such a composite a true synthetic replacement for autogenous cancellous bone.

Animals↗

Phase development and structural characterization of calcium phosphate ceramics-polyacrylic acid nanocomposites at room temperature in water-methanol mixtures.

Calcium phosphate ceramics (CPCs) were prepared via an in-situ formation in the presence of polyacrylic acid (PAA) polymer under water-methanol (WM) mixture at room temperature. The PAA polymer was employed as both structure-directing agent and crystallization retardant to manipulate the development of resulting CPCs nano-crystallites which are observed to show a core-shell configuration with a thin layer of PAA molecules. A resulting phase evolution map with respect to the developing phases of calcium-deficient hydroxyapatite (CDHA), beta-tricalcium phosphate (beta-TCP), and an intermediate amorphous calcium phoshate (ACP) that were structurally and spectroscopically identified, was constructed in terms of fractions of water-to-methanol proportions and concentration of PAA. It is found that for the solutions in both water-rich and methanol-rich regions, pure CDHA and beta-TCP instead of intermediate ACP phase can be developed irrespective of the concentration of PAA, respectively. For conditions in between, i.e., with methanol fractions of 15%-90%, ACP appeared only when the PAA fell in a limited concentration range.

Acrylic Resins↗

Evaluation of chitosan/beta-tricalcium phosphate microspheres as a constituent to PMMA cement.

Two methods, a traditional emulsion technique and a high voltage electrostatically modified encapsulation system, were used to fabricate degradable chitosan/beta -tricalcium phosphate (beta-TCP) microspheres. The two distinct kinds of microspheres both exhibited good sphericity and the beta-TCP was trapped well inside the chitosan gel. The microspheres prepared by high voltage electrostatic system exhibited a rougher outer surface and narrower size distribution. These microspheres were then used as an added constituent to commercially available PMMA bone cement. Four modified cement composites that were prepared with different composition ratios of the two kinds of chitosan/beta-TCP microspheres that were made from emulsion technique (C1P1 and C2P1) and from a process by a high voltage electrostatic system (EC1P1 and EC2P1) were compared with the PMMA cement (Pure P). The characteristics of these materials indicate that with the addition of chitosan/beta-TCP microspheres as a constituent into the PMMA cement significantly decreases the curing peak temperature. Furthermore, the setting time increases from 3.5 min to 9 min, as compared to the PMMA cement. These changes could be beneficial for the handling of the bone cement paste and causing less damage to the surrounding tissues. Understandably, the presence of chitosan/beta-TCP microspheres in the prepared composites reduced the ultimate compressive strength and bending strength. From the degradation test and SEM observations, the modified chitosan/beta -TCP/PMMA composites could be degraded gradually and create rougher surfaces that would be beneficial to cell adherence and growth.

Biocompatible Materials↗

Sonochemical synthesis of calcium phosphate powders.

beta-tricalcium phosphate (beta-TCP) and biphasic calcium phosphate powders (BCP), consisting of hydroxyapatite (HA) and beta-TCP, were synthesized by thermal decomposition of precursor powders obtained from neutralization method. The precursor powders with a Ca/P molar ratio of 1.5 were prepared by adding an orthophosphoric acid (H(3)PO(4)) solution to an aqueous suspension containing calcium hydroxide (Ca(OH)(2)). Mixing was carried out by vigorous stirring and under sonochemical irradiation at 50 kHz, respectively. Glycerol and D-glucose were added to evaluate their influence on the precipitation of the resulting calcium phosphate powders. After calcination at 1000 degrees C for 3 h BCP nanopowders of various HA/beta-TCP ratio were obtained.

Biocompatible Materials↗

The copolymer of epsilon-caprolactone-lactide and tricalcium phosphate does not enhance bone growth in mandibular defect of sheep.

In the field of craniomaxillofacial and orthopaedic surgery there is a constant need for bone or bone substitute. At the present, the most effective way to enhance bone healing clinically is to use autogenous bone grafts. The problems associated with the use of these autografts are donor site morbidity, limited supply and need for a second operative site. Currently there are several different synthetic products commercially available in the market; nevertheless, none of them is ideal for filling bone defects. Therefore, search for new synthetic materials for bone replacement is necessary. A mixture of tricalcium phosphate (TCP) and epsilon-caprolactone-lactide copolymer P(epsilon -CL/DL-LA) was prepared and implanted in critical size mandibular bone defects in twelve sheep. Contralateral side was used as a control. Follow-up times for histological and radiological studies were 9, 14, 24 and 52 weeks. We found that the implanted material did not enhance bone formation compared to control site. We also confirmed that defect size was of critical size, since there was no complete healing of the control site either. The results do not encourage us to continue our studies with the mixture of TCP and P(epsilon-CL/DL-LA) as a filling material for bone defects. Therefore the search for the ideal material is still ongoing.

Animals↗

Biodegradable and semi-biodegradable composite hydrogels as bone substitutes: morphology and mechanical characterization.

Biodegradable and semi-biodegradable composite hydrogels are proposed as bone substitutes. They consist of an hydrophilic biodegradable polymer (HYAFF 11) as matrix and two ceramic powders (alpha-TCP and HA) as reinforcement. Both components of these composites have been of great interest in biomedical applications due to their excellent biocompatibility and tissue interactions, however they have never been investigated as bone substitute composites. Morphological and mechanical analysis have shown that the two fillers behave in a very different way. In the HYAFF 11/alpha-TCP composite, alpha-TCP is able to hydrolyze in contact with water while in the HYAFF 11 matrix. As a result, the composite sets and hardens, and entangled CDHA crystals are formed in the hydrogel phase and increases in the mechanical properties are obtained. In the HYAFF11/HA composite the ceramic reinforcement acts as inert phase leading to lower mechanical properties. Both mechanical properties and microstructure analysis have demonstrated the possibility to design hydrophilic biodegradable composite structures for bone tissue substitution applications.

Biocompatible Materials↗

The impact on oncology of the interaction of radiation therapy and radiobiology.

The quantitative analysis of the cell dose-survival curves, the randomness of cell killing by radiation, the probabilistic basis of the response to irradiation of tumors and normal tissues, the understanding of the biological mechanisms underlying to this response, the rationale for dose-time and fractionation in radiotherapy, the introduction of the concepts of tumor control probability (TCP) and biologically effective dose (BED), the relationships TCP-dose, BED-alpha/beta BED-fraction size and BED-treatment time, the problems associated with the accelerated regeneration of surviving tumor clonogens during the course of fractionated radiotherapy, the new demands of knowledge on oncology and radiation biology derived from heterogeneous dose distributions in conformal radiation therapy programs and the definition of the biological basis of normal tissues tolerance to reirradiation are, probably, the most important contributions of radiobiology to clinical radiotherapy in the last twenty five years. Radiotherapy is today a scientific discipline based on the interplay of mathematics, physics, biology and oncology. The knowledge of the basic concepts of radiobiology is essential for daily radiotherapy practices and for all oncologists. The most efficient use of multimodality treatments in cancer therapy cannot be done without a clear understanding of these principles.

Apoptosis↗

The rat brain phencyclidine (PCP) receptor. A putative K+ channel.

Receptor binding studies were carried out to test whether the rat brain phencyclidine (PCP) receptor is part of a K+ channel. [3H]PCP, and two analogs, [3H]TCP and m-amino[3H]PCP, labeled a single receptor on rat brain synaptic membranes. Each compound bound to a similar number of sites (Bmax = 2.7 pmol bound/mg protein); the apparent dissociation constants for these compounds (KD less than 0.3 microM) decreased with increasing temperature. The following observations indicate that the PCP receptor is part of a K+ channel: (1) aminopyridines (AP) and tetraalkylammonium ions blocked [3H]PCP binding; their respective orders of potency, 4-AP = 3,4-diAP much greater than 3-AP, and tetrabutylammonium (TBA) greater than tetraethylammonium much greater than tetramethylammonium, paralleled their abilities to block K+ channels, (2) the order of potency of PCP and its analogs for binding to the PCP receptor, TCP greater than PCE greater than m-amino-PCP greater than PCP greater than PCPY greater than m-nitro-PCP, paralleled their rank order for blocking brain K+ channels, and (3) the stereospecific displacement of [3H]PCP binding by the isomers of the "sigma" ligands, (+)N-allyl-normetazocine (NANM) greater than (-)NANM, and (-)cyclazocine greater than (+)cyclazocine, and of the dioxolanes, dexoxadrol much greater than levoxadrol, paralleled their abilities to block brain K+ channels. Reciprocal plot and Schild plot analyses indicated that TBA, (+)NANM and dexoxadrol were competitive inhibitors at the PCP receptor, whereas 4-AP had an allosteric interaction.

Animals↗

Differential effects of antidepressants on GABAB and beta-adrenergic receptors in rat cerebral cortex.

The effects of chronic administration of antidepressant drugs on beta-adrenergic and gamma-amino-butyric acid (GABA)B receptors have been assessed with radioligand binding. Tricyclics [imipramine (IMI), 30 mg/kg/day, and desmethylimipramine (DMI), 10 mg/kg day] or monoamine oxidase inhibitors [(+/-)-tranylcypromine (TCP), 1 mg/kg/day, and phenelzine (PLZ), 10 mg/kg/day] were administered to male Sprague-Dawley rats by constant infusion via Alzet 2ML4 osmotic minipumps for 28 days. Pumps were implanted s.c. in the interscapular region. On day 28 the animals were killed and their brains removed; [3H]GABA binding to GABAB receptors was measured in frontal cortex and the remaining cortical tissue was used to measure [3H]dihydroalprenolol ([3H]DHA) binding to beta-adrenoceptors. All drugs tested induced a significant decrease in density (Bmax) of [3H]DHA binding, although no significant changes in affinity (Kd) were observed. [3H]GABA binding was not altered significantly by chronic antidepressant treatment. TCP-treated animals showed a tendency towards increased [3H]-GABA binding, but the differences did not reach statistical significance. No effects on Kd were observed. These data do not support the proposal that an increase in the total population of cortical GABAB receptors is a common effect of chronic antidepressant treatment.

Animals↗

An endogenous ligand of the brain sigma/PCP receptor antagonizes NMDA-induced neurotransmitter release.

The present study provides evidence for the presence of an endogenous ligand for the phencyclidine (PCP) receptor of mammalian brain. Partially purified bovine hippocampal extracts potently and dose dependently inhibit binding to PCP receptors of [3H]N-(1-[2-thienyl]-cyclohexyl)piperidine (TCP), a highly potent and specific ligand of PCP receptors. In addition to demonstrating PCP-like binding properties, the partially purified extract mimics biological actions of PCP upon neurotransmitter release. HPLC fractions active in the [3]TCP binding assay, by contrast to fractions inactive in the binding assay, potently elicited stimulation of spontaneous acetylcholine and dopamine efflux and inhibited NMDA-stimulated release of acetylcholine and dopamine. The transmitter release assay provides validation of a PCP-like physiological activity exerted by bovine hippocampal extracts partially purified by HPLC.

Acetylcholine↗

The novel anticonvulsant MK-801: a potent and specific ligand of the brain phencyclidine/sigma-receptor.

MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) is a novel anticonvulsant agent reported to antagonize certain N-methyl-D-aspartate (NMDA)-mediated effects non-competitively. The question arises of the mechanism underlying the anti-NMDA and anticonvulsant effects of MK-801. In the present study MK-801 is shown to be an extremely potent inhibitor of the binding of N-[3H] (1-[2-thienyl]cyclohexyl)piperidine ([3H]TCP) to brain phencyclidine (PCP)/sigma-receptors. Its IC50 value of 3.8 +/- 0.8 nM in this assay ranks it as the most potent known ligand of brain PCP/sigma-receptors. Addition of MK-801 altered the apparent Kd but not the apparent Bmax values for [3H]TCP binding, indicating a competitive interaction. The specificity of action of MK-801 is supported by the finding that MK-801 strongly inhibited the binding of (+)-N-[3H]allylnormetazocine ((+)-[3H]SKF 10,047) to the PCP/sigma-receptor but its effect on (+)-[3H]SKF 10,047 binding to the non-PCP, haloperidol-sensitive sigma-binding site was weaker by several orders of magnitude. Furthermore, MK-801 exerts PCP-like antagonistic effects upon NMDA-induced [3H]norepinephrine release. These findings support the concept that the anticonvulsant and anti-NMDA effects of MK-801 result from its being the most potent known ligand of PCP/sigma-receptors.

Animals↗

Linkage between phencyclidine (PCP) and N-methyl-D-aspartate (NMDA) receptors in the cerebellum.

It has been suggested that phencyclidine (PCP) receptors may not be linked with N-methyl-D-aspartate (NMDA) receptors in all brain areas. We found that NMDA enhanced [3H]TCP (a PCP analog) binding in extensively washed cortical, but not cerebellar membranes. However, PCP potently inhibited NMDA-induced [3H]norepinephrine release from cerebellar slices in a concentration-dependent manner, suggesting that a subtype of cerebellar PCP receptors is functionally linked with NMDA receptors. It is suggested that this subtype cannot be demonstrated by [3H]TCP binding because of the predominance of low affinity PCP receptors in the cerebellum.

Animals↗

Glycine modulation of the phencyclidine binding site in mammalian brain.

Neurophysiological studies have shown that glycine potentiates the NMDA response in cultured neurons by a strychnine-insensitive mechanism. Autoradiographic data have demonstrated a correspondence between strychnine-insensitive [3H]glycine binding sites and NMDA-sensitive [3H]glutamate binding sites. Here we report that in synaptic plasma membranes from rat brain, the binding of a PCP analog, [3H]TCP, was enhanced more than 5-fold by 1 microM glycine. This glycine stimulation of binding of [3H]TCP was blocked by the competitive NMDA-receptor antagonist, D-AP7. These data provide support for the hypothesis that a unique amino acid recognition site is associated with the proposed NMDA/PCP receptor complex in brain.

Animals↗

Frontal decortication decreases the affinity of N-(1-[2-thienyl]cyclohexyl)[3H]piperidine binding to rat striatum.

Bilateral ablation or transection of the corticostriatal pathways of the rat caused a reduction in N-(1-[2-thienyl]cyclohexyl)[3H]piperidine ([3H]TCP) binding to the striatum at 5-7, but not 3 and 14-28, days postlesion with a persistent decrease in striatal glutamate content 3-28 days after the decortication. This reduction was found to be due to an increase in Kd without changes in Bmax of the [3H]TCP binding. The present findings suggest that interruption of striatal glutamatergic transmission following frontal decortication may produce a temporal reduction in the affinity of phencyclidine receptor in the striatum.

Animals↗