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At least 811 records · Page 45Linked to original sources
PubMed2003

Biomimetic PMMA-based bone substitutes: a comparative in vitro evaluation of the effects of pulsed electromagnetic field exposure.

Pulsed electromagnetic fields (PEMFs) are known to be effective in the stimulation of cultured osteoblasts and in vivo healing of delayed and nonunion fractures. In the present in vitro study the effects of PEMFs on osteoblastic cell cultures (MG63 human osteoblast-like cells) grown in the presence of poly-methylmethacrylate (PMMA) and of a biomimetic bone substitute made of a PMMA matrix added with alfa-tricalcium phosphate (PMMA+alpha-TCP) were evaluated, to assess the biological response at the cell-biomaterial interaction. Cultures were stimulated with PEMFs (75 Hz, 2.3 mT, 1.3-ms pulse duration) 12 h/day for 3 days and evaluations (MTT, ALP, OC, PICP, TGFbeta-1, IL-6) were performed at 3 and 6 days. PMMA had a negative effect on osteoblasts, whereas PMMA+alpha-TCP enhanced production of ALP, PICP, OC and TGFbeta-1, and reduced IL-6 levels. Cells responded positively to PEMF stimulation even when cultured with a poorly biocompatible material, such as PMMA. This effect was more evident in the presence of PMMA+alpha-TCP (further improvement in proliferation and synthetic activity) both at 3 and at 6 days. The properties of PMMA+alpha-TCP look promising, and the present results support the use of PEMFs to improve tissue response to biomaterials implanted as bone substitutes.

Bone Substitutes↗
PubMed2004

Effect of rapidly resorbable calcium phosphates and a calcium phosphate bone cement on the expression of bone-related genes and proteins in vitro.

The use of biodegradable bone substitutes is advantageous for alveolar ridge augmentation because it avoids second-site surgery for autograft harvesting. This study examines the effect of novel, rapidly resorbable calcium phosphates and a calcium phosphate bone cement on the expression of bone-related genes and proteins by human bone-derived cells (HBDCs) and compares this behavior to that of tricalciumphosphate (TCP). Test materials were alpha-TCP, two materials with a crystalline phase Ca(2)KNa(PO(4))(2) and with a small amorphous portion containing either magnesium potassium phosphate (material denominated GB14) or silica phosphate (material denominated GB9), and a calcium phosphate bone cement (material denominated Biocement D). HBDCs were grown on the substrata for 3, 7, 14, and 21 days, counted, and probed for various mRNAs and proteins (type I collagen, osteocalcin, osteopontin, osteonectin, alkaline phosphatase, and bone sialoprotein). All substrates supported continuous cellular growth for 21 days. In the presence of GB14 and Biocement D specimens cell proliferation was reduced and cell differentiation increased. At day 21, the greatest number of cells was found on GB9 expressing significantly higher levels of bone-related proteins than cells grown on all other surfaces. Because all novel materials facilitated the expression of the osteoblastic phenotype at least as much as TCP and the polystyrene control, these biomaterials can be regarded as excellent candidate bone substitute materials. GB9 induced the highest proliferation and cellular differentiation after 21 days of incubation, suggesting that this material may possess a higher potency for enhancing osteogenesis than TCP.

Adolescent↗
PubMed2004

Effect of controlled zinc release on bone mineral density from injectable Zn-containing beta-tricalcium phosphate suspension in zinc-deficient diseased rats.

The purpose of this study was to evaluate the efficacy of zinc (Zn)-containing beta-tricalcium phosphate (Zn-TCP) in correcting the bone mineral deficiency noted in osteoporosis using ovariectomized rat model. Four rats were used for each of the four experimental groups: D0, D10, D20, and N10. The rats in D0, D10, and D20 groups were ovariectomized, and fed a vitamin D-, Ca-, and Zn-deficient diet, and induced Zn-deficient osteoporoses for 9 weeks. In contrast, the N10 group was the normal rats fed normal healthy diet for 9 weeks. D0 group was injected with pure beta-TCP suspension, D10 and D20 groups were injected with suspensions containing 10 mg of 10 mol % (6.17 wt % Zn) and 20 mol % (12.05 wt % Zn) Zn-TCP, respectively, and the healthy group, N10 were injected with 10 mol %. Zn-TCP suspensions. Injections were administered intramuscularly in the left thigh once a week in all rats, and fed a vitamin D- and Zn-deficient diet for 9 weeks. The plasma calcium (Ca) and Zn levels, plasma alkaline phosphatase activity (ALP) and bone mineral density (BMD) of the lumbar vertebra and femora were measured. The plasma Zn levels in all the rats were between 1.1 and 2.8 microg/mL. The areas under the curves for the Ca, Zn, and ALP (Ca-AUC, Zn-AUC, and ALP-AUC) levels between 0 and 63 days were calculated. Results for the AUCs were as follows: (1) the Zn-AUCs were in the order of N10 = D20 > D10 > D0; (2) the Ca-AUCs for D0, D10 groups were significantly lower than that for the N10 group; (3) the ALP-AUCs for the D10 and D20 groups were significantly higher than that for the N10 group, and that of the D0 group was in between those. The body weight of D10 and D20 groups significantly increased with time, that of the D0 group increased slightly, and that of the N10 group remained unchanged for the entire experimental period. The BMD of the lumbar vertebrae of the D10 and D20 groups (about 100 mg/cm(2)) was significantly higher than that of the D0 group but lower than that of the N10 group. The BMD of the left femur increased more than that of the right femur with the increase in the amount of Zn in the suspension. The results of this study suggest that the local effect on BMD was more pronounced than the effect on the whole body.

Alkaline Phosphatase↗
PubMed2006

In vivo study of novel biodegradable and osteoconductive CaO-SiO2-B2O3 glass-ceramics.

To evaluate the possibility of novel CaO-SiO2-B2O3 glass-ceramics (CS10B) as a new bone replacement material, we compared the biodegradation and osteoconduction properties of CS10B, hydroxyapatite (HA), and tricalcium phosphate (TCP). Porous CS10B implants were prepared by the polymer sponge method. L5-6 single-level posterolateral spinal fusions were performed on 30 New Zealand white male rabbits. The animals were divided into three groups by implant material: CS10B, HA, and TCP. Radiographs were performed every 2 weeks. All animals were euthanized 12 weeks after surgery. The ratio of the area occupied by the ceramics by final and initial radiographs was calculated using radiomorphometric analysis. Uniaxial tensile strength was determined from seven cases in each group. The ratio of the area occupied by HA (88.7%+/-16.1%) was significantly higher than the others (p<0.005), and the ratio of the area occupied by CS10B (28.2%+/-9.3%) was significantly lower than those of HA and TCP (37%+/-9.6%, p<0.05). The mean values of the tensile strengths of the CS10B (182.7+/-19.9 N) and HA (191.4+/-33.5 N) were significantly higher (p<0.05) than that of TCP (141.1+/-28.2 N). CS10B had a fusion mass tensile strength similar to that of HA. Histological analysis confirmed that CS10B was well incorporated into the fusion mass. These findings suggest that CS10B is a possible bone replacement material.

Animals↗
PubMed2006

Bone formation using human adipose tissue-derived stromal cells and a biodegradable scaffold.

Human adipose tissue, obtained by liposuction, was processed to obtain a fibroblast-like population of cells or adipose tissue-derived stromal cells (ATSCs). The ATSCs, as well as bone marrow-derived mesenchymal stem cells (BMSCs), have the capacity for renewal and the potential to differentiate into multiple lineages of mesenchymal tissues. These cells are capable of forming bone when implanted ectopically in an appropriate scaffold. The aim of this study was to evaluate a beta-tricalcium phosphate (beta-TCP) as a scaffold and to compare the potential of osteogenic differentiation of ATSCs with BMSCs. Both cell types were loaded into beta-TCP disk and cultured in an osteogenic induction medium. Optimal osteogenic differentiation in ATSCs in vitro, as determined by secretion of osteocalcin, scanning electron microscope, and histology, were obtained in the culturing with the beta-TCP disk. Furthermore, bone formation in vivo was examined by using the ATSC- or BMSC-loaded scaffolds in nude mice. The present results show that ATSCs have a similar ability to differentiate into osteoblasts and to synthesize bone in beta-TCP disk as have BMSCs.

Adipose Tissue↗
PubMed1988

Bone ingrowth into porous calcium phosphate ceramics: influence of pulsing electromagnetic field.

The effect of a pulsing electromagnetic field (PEMF) on bone ingrowth into porous hydroxyapatite (HA) and porous tricalcium phosphate (TCP) implanted in rabbit tibiae was studied. To quantitate the biological response, a recently developed method of surface measurement using a scanning electron microscope was used. The morphometrical findings in the HA pores demonstrated a significantly greater amount of bone and thicker bone trabeculae in the PEMF group as compared with the nonpulsed control group at 3 to 4 weeks postimplantation. No significant differences for these parameters were found in the TCP pores. Histologically, more bone and wider bone trabeculae were observed in the HA implants for the PEMF-treated animals at the early time periods when compared with those of the control animals. Alternatively, the histological findings of the TCP implants were similar between these two groups. These histological results tended to correlate with the morphometrical data. Together, these results suggest that accelerated bone formation and bone maturation occurred in response to PEMF in the HA pores but was without effect in the TCP pores. This stimulatory effect is most significant after 3-4 weeks of PEMF stimulation.

Animals↗
PubMed2007

In vitro study comparing two collageneous membranes in view of their clinical application for rotator cuff tendon regeneration.

Tenocytes were isolated from the rotator cuff tendons of healthy (HT) and glucocorticoid (GC)-treated rats (GCT) and were cultured on polystyrene wells (TCP) as control, and on 2 de-cellularized collagen matrices: porcine small intestinal submucosa (SIS), and human dermal matrix (Graftjacket, GJ). At 3 and 7 days cell proliferation and synthesis were evaluated. Proliferation of HT tenocytes increased between experimental times for both tested membranes, but already at 3 days, HT tenocytes cultured on GJ showed the highest WST-1 value. The collagen-I (CICP) synthesis on GJ membrane did not change between experimental times and was significantly higher than TCP and SIS at 7 days. Proteoglycans (PG), and fibronectin (FBN) synthesis increased when HT were cultured on GJ, between experimental times, and both PG and FBN synthesis on GJ membrane were higher than TCP and SIS at 7 days. GC determined decreases in cell proliferation, CICP and PG syntheses at 3 days of culture on TCP when compared to HT tenocytes while a decrease in WST-1 was maintained at 7 days. CICP, PG and FBN (only at 3 days) syntheses were significantly higher in GCT tenocytes cultured on GJ. The negative effects on GC on GCT tenocytes cultured on membrane were particularly evident on SIS for CICP (-18%) and FBN (-67%) synthesis. The obtained results support the conclusion that GJ is more suitable than SIS as a scaffold for in situ tissue engineering and for the in vitro bioengineering of tendons to heal massive tears of the rotator cuff tendon.

Animals↗
PubMed1989

Phencyclidine and sigma receptors in rat spinal cord: binding characterization and quantitative autoradiography.

These experiments were designed to compare phencyclidine (PCP) and sigma (sigma) receptor binding sites in the rat spinal cord by using receptor binding and autoradiographic techniques. Binding sites for 3H-TCP (3H-1-[1-(2-thienyl)cyclohexy]piperidine), a PCP receptor agonist, and (+)3H-3-PPP (3H-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine), a sigma receptor agonist, in the rat spinal cord were shown to represent two populations of recognition sites. Inhibition studies revealed that ligands with high affinity for the PCP receptor (MK-801 and PCP) were potent competitors at 3H-TCP binding sites whereas the putative sigma receptor ligands (+/-)pentazocine and haloperidol were potent competitors at (+)3H-3-PPP binding sites. The autoradiographic distribution of 3H-TCP and (+)3H-3-PPP binding sites in adjacent sections of rat spinal cord demonstrated the occurrence of two distinct populations of binding sites. 3H-TCP binding sites were localized primarily in laminae I and II in cervical and thoracic spinal segments. Binding sites in lamina I decreased in density along a rostral to caudal gradient in the spinal cord. The highest density of (+)3H-3-PPP binding sites was found in the ventral horn (lamina VIII and IX) and over perikarya in dorsal root ganglia. Significantly elevated densities of (+)3H-3-PPP binding sites were also found in lamina X within thoracic and lumbar segments and in the intermediolateral cell column. The results of the present study show that PCP and sigma receptor binding sites are differentially localized in the rat spinal cord and suggest that separate binding sites exist for PCP and sigma agonists.

Animals↗
PubMed1997

Effects of hypoxia on valve-closure time and bioaccumulation of 2,4,5-trichlorophenol by the freshwater clam Sphaerium corneum [L].

The effects of hypoxia and 2,4,5-trichlorophenol (TCP) on the behavior of the freshwater clam Sphaerium corneum (L.) and the accumulation and elimination rates of 2,4,5-trichlorophenol were studied in the laboratory at 20 degrees C. After an initial high activity period, the shell valves were held closed for significantly longer periods in hypoxia than in normoxia. At the end of the 36-hr exposure period, the number of individuals with closed valves increased under normoxic conditions as well. The accumulation of TCP into clam tissues in normoxia was rapid and an uptake rate constant of 27.97 (+/-6.64) ml/g/hr was measured. An apparent steady state was achieved within 12 to 24 hr and the bioconcentration factors varied between 115 and 139. The depuration rate constant (kd) based on the accumulation data was 0.2717 (+/-0.07) hr-1. However, the much lower kd of 0.0137 (+/-0.0019) hr-1 measured over the depuration period from 24 to 120 hr suggests biphasic depuration kinetics. After a 6-hr exposure to TCP in both hypoxia and normoxia, the highest body burdens were found in clams exposed under normoxic conditions. A significant correlation was found between body burden and length of time the valves were open during the exposure. Results suggest that in short-term experiments, S. corneum can reduce the bioaccumulation of TCP by closing their shell valves.

Anaerobiosis↗
PubMed1997

Effect of Mixing Entropy on the Static Yield Stress of a Liquid Dispersion of Solid Particles: Comparison between Si3 N4 and Ca3 (PO4 )2 Aqueous Suspensions

Experimental measurements of the static yield stresses tau of silicon nitride (SN, Si3 N4 ) and alpha-tricalcium phosphate (TCP, alpha-Ca3 (PO4 )2 ) aqueous dispersions have been performed for different pH values of the liquid medium and, as a result, the two tau vs pH behaviors are quite different. In agreement with the DLVO theory, the static yield stress value for silicon nitride is maximal at the isoelectric point of the slurry (pHiep (SN) = 8.0 &plusmn; 0.1) and, for higher and/or lower suspension pH values, it decreases progressively. On the other hand, in tricalcium phosphate dispersed systems, the maximum value of tau is not observed at the isoelectric point (pHiep (TCP) = 6.7 &plusmn; 0.1) but two relative maximum values, taua and taub , are observed for two suspension pH values in the acid/basic environments, namely, for pH <> pHiep (TCP) . First, displacements of the pH from the isoelectric point in both environments are accompanied by an increase in tau; second, after the maximum tau values have been reached, the static yield stress decreases with the increase in the [H+ ]/[OH+ ] ions in the solution. It is shown that this phenomenon can be interpreted as an effect of the mixing entropy relative to the solid TCP aggregates, which is very sensitive to the suspension pH. Phenomenological and theoretical explanations are developed, respectively, by a heuristic recasting of the Hamaker expression for the London-van der Waals forces and by a relationship between the static yield stress and the number of solid aggregates; this relation is based on recently proposed methods for investigating the agglomeration/adsorption phenomena in a dispersed system.

Journal Article↗
PubMed1997

Chlorpyrifos, parathion, and their oxons bind to and desensitize a nicotinic acetylcholine receptor: relevance to their toxicities.

The nicotinic acetylcholine receptor (nAChR) of the electric organ of the electric ray. Torpedo sp., the richest source of nAChR, with similar structure and pharmacology to the mammalian skeletal muscle nAChR, carries several binding sites for different ligands. Incubation of Torpedo membrane-bound nAChRs with the agonist carbamylcholine (Carb) stimulated the binding of [3H]thienyl-cyclohexylpiperidine ([3H]TCP), which binds to the receptor's noncompetitive antagonist binding site in its ionic channel, with high affinity (Kd of 196 nM). The agonist-stimulated binding of [3H]TCP (i.e., binding to activated nAChRs) was inhibited in a concentration-dependent manner by four organophosphate (OP) anticholinesterases, chlorpyrifos oxon (CPO), chlorpyrifos (CPS), parathion (PS), and paraoxon (PO) with IC50 (concentration that inhibits 50% of the effect) values of 5, 150, 200, and 300 microM, respectively. The binding of CPO was totally reversible. The OPs had no effect on equilibrium binding of [alpha-125I]bungarotoxin ([alpha-125I]BGT) to the receptor's acetylcholine (ACh)-binding site, but preincubation of the membranes with the OPs increased this site's affinity for Carb. In absence of agonist, 100 microM of the OPs increased the binding of [3H]TCP by two- to fivefold with the following order of decreasing potency: PS > CPO > CPS > PO. The data suggest that in addition to inhibition of acetylcholinesterase, these OPs bind to a site on the nAChR that is different from the sites that bind ACh or TCP and that this binding induces nAChR desensitization. The relevance of this direct action of OPs on nAChRs on their acute toxicities is discussed.

Animals↗
PubMed2002

Noncholinesterase mechanisms of chlorpyrifos neurotoxicity: altered phosphorylation of Ca2+/cAMP response element binding protein in cultured neurons.

Previous studies suggest that low doses of the organophosphate insecticide chlorpyrifos (CPF) disrupt brain development and cognitive function by mechanisms that do not involve the inhibition of acetylcholinesterase (AChE). In the present study we tested the hypothesis that CPF and its metabolites alter the Ca2+/cAMP response element binding protein (CREB), a critical molecule in brain development and cognitive function. We further tested the hypothesis that changes in CREB occur independent of AChE inhibition. Western blot analysis of lysates from primary cultures of cortical neurons exposed to CPF, CPF-oxon, or trichloropyridinol (TCP) for 1 h and cultures exposed to trichloropyridinol (TCP) for 7 days indicated that all exposures increased the level of the phosphorylated (activated) form of CREB (pCREB), without significant changes in total CREB or alpha-tubulin. Remarkably, pCREB in cortical neurons was elevated by 300-400% of control levels with estimated EC50s of 60 pM, <30 fM, and <30 pM for CPF, CPF-oxon, and TCP, respectively. AChE activity and cell viability were not affected by organophosphate concentrations that caused significant increases in pCREB (up to 100 nM, 100 pM, and 10 microM of CPF, CPF-oxon, and TCP, respectively). The level of pCREB in hippocampal neurons was also elevated after exposure to CPF, but pCREB in cultured astrocytes was not affected. Inclusion of the cytochrome P-450 inhibitor SKF-525A did not inhibit the effects of CPF on pCREB levels, indicating that metabolism of CPF to CPF-oxon was not necessary to cause the increase in pCREB. The increases in neuronal pCREB observed in this study provide biochemical evidence that CPF and its metabolites are active at critical sites within the nervous system at levels far below those required to inhibit AChE, which could explain many of the reported neurodevelopmental and behavioral changes attributed to CPF toxicity.

Acetylcholinesterase↗
PubMed1995

Biodegradation of chlorophenols by mixed and pure cultures from a fluidized-bed reactor.

An aerobic, continuous-flow fluidized-bed reactor was established with inoculum from activated sludge, and fed a mixture of 2,4,6-trichlorophenol (TCP), 2,3,4,6-tetrachlorophenol (TeCP) and pentachlorophenol (PCP) as the sole sources of carbon and energy for 2 years. Experiments with the enrichment were performed with material from the reactor. Later, degradation experiments were completed using pure cultures of bacteria that were isolated from suspended samples of the carrier biofilm. In batch-bottle bioassays, the reactor enrichment degraded PCP, TeCP and TCP both in mineral salts (MS) and tryptone-yeast extract-glucose (TGY) media. ortho-Methoxylated chlorophenols including 4,5-dichloroguaiacol (4,5-DCG), tetrachloroguaiacol (TeCG) and trichlorosyringol (TCS) resisted biodegradation by the enrichment both in MS and TGY media, whereas 5,6-dichlorovanillin (5,6-DCV) was readily transformed to an unidentified metabolite. Experiments with 14C labeled chlorophenols showed mineralization of 2,4-dichlorophenol (DCP) and 2,3,5-TCP to 14CO2 by the enrichment. Material from the suspended biofilm after continuous chlorophenol feeding for 2 years was inoculated onto TGY-agar plates, and showed predominantly two colony types accounting for over 99% of the total colony counts. The two colony types, were equal in abundance. Six Gram-negative, oxidase- and catalase-positive, nonfermentative small rods were isolated in TGY agar media supplemented with 10 mg/l of TeCP or PCP. All isolates formed colonies in TGY plus 150 mg/l of PCP. The isolates degraded TCP and TeCP but not PCP. In mixtures of isolated bacteria the rates of chlorophenol degradation were similar to those observed with individual isolates. Three isolates were identified as Pseudomonas saccharophila and three were an unidentified species of Pseudomonas.

Biodegradation, Environmental↗
PubMed1992

Functional analysis of a t complex responder locus transgene in mice.

Transmission ratio distortion (TRD) of mouse t haplotypes occurs through the interaction of multiple distorter loci with the t complex responder (Tcr) locus. Males heterozygous for a t haplotype will transmit the t-bearing chromosome to nearly all of their offspring. This process is mediated by the production of functionally inequivalent gametes: wild-type meiotic partners of t spermatozoa are rendered functionally inactive. The Tcr locus, which is required for TRD to occur, is thought to somehow protect its host spermatid from the sperm-inactivating effects of linked distorter genes (Lyon 1984). In previous work, Tcr was mapped to a small genetic interval in t haplotypes, and a candidate gene from this region was isolated (Tcp-10bt). In this work, we further localize Tcr to a 40-kb region that contains the 21-kb Tcp-10bt gene. A cloned genomic copy of Tcp-10bt was used to generate transgenic mice. The transgene was bred into a variety of genetic backgrounds to test for non-Mendelian segregation. Abberrant segregation was observed in some mice carrying either a complete t haplotype or a combination of certain partial t haplotypes. These observations, coupled with those of Snyder and colleagues (in this issue), provide genetic and functional evidence that the Tcp-10bt gene is Tcr. However, other genotypes that were predicted to produce distortion did not. The unexpected data from a variety of crosses in this work and those of our colleagues suggest that elements to the TRD system and the Tcr locus remain to be identified.

Animals↗
PubMed1992

Distortion of transmission ratio by a candidate t complex responder locus transgene.

The mouse t complex responder locus (Tcr) is centrally involved in the phenomenon of male-specific transmission ratio distortion (TRD) through its action in haploid germ cells. Previously, we identified a candidate gene, Tcp-10b, whose t allele generates alternatively spliced transcripts. The full-length Tcp-10bt transcript is present in pre- and postmeiotic germ cells and encodes a product that is virtually identical with that encoded by the wild-type allele. The alternatively spliced t-specific transcript is observed in post-meiotic haploid spermatids and would encode an altered polypeptide that could convey the Tcrt phenotype. To assess their function, we have introduced constructs representing each Tcp-10bt transcript into transgenic mice. Breeding experiments demonstrate that these two constructs alter the transmission ratios of t haplotypes from male mice, but in opposite directions. The results provide support for the hypothesis that Tcp-10bt is a component of the Tcr locus.

Animals↗
PubMed1992

MPTP lesions of the nigrostriatal dopaminergic projection decrease [3H]1-[1-(2-thienyl)cyclohexyl]piperidine binding to PCP site 2: further evidence that PCP site 2 is associated with the biogenic amine reuptake complex.

Our previous studies have demonstrated that, using membranes of guinea pig brain, [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) labels not only the phencyclidine binding site associated with the NMDA receptor (PCP site 1), but also a second high affinity binding site which is associated with the biogenic amine reuptake carrier (termed PCP site 2). To test this hypothesis, the binding of [3H]GBR12935 to the dopamine transporter, and [3H]TCP binding to PCP sites 1 and 2 were measured in caudates harvested from control, MPTP-treated and reserpine-treated dogs. MPTP treatment decreased dopamine levels by over 99%, decreased [3H]GBR12935 binding by over 90%, decreased [3H]TCP binding to PCP site 2 by about 50%, and had no significant effect on [3H]TCP binding to PCP site 1. These data are consistent with the hypothesis that a portion of PCP site 2 is associated with dopaminergic nerve terminals in dog caudate.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Effects of low- and high-dose tranylcypromine on [3H]tryptamine binding sites in the rat hippocampus and striatum.

Chronic studies were initiated in rats to determine the effects of high- and low-dose tranylcypromine (TCP) on [3H]tryptamine (3H-T) binding sites. Male Sprague-Dawley rats were administered TCP (0.5 or 2.5 mg/kg/day) or vehicle (distilled water) for 4, 10 or 28 days via Alzet minipumps. After decapitation, the hippocampus and striatum were used to prepare membrane fragments for single point 3H-T binding. Hippocampal 3H-T binding was reduced after 10 and 28 days with the low dose and after 4, 10 and 28 days with the high dose. Striatal 3H-T binding was reduced by both doses at all time intervals. The high dose resulted in a significantly greater reduction in striatal 3H-T binding than did the low-dose after 4, 10, and 28 days. These results suggest that a more rapid reduction of 3H-T binding in the hippocampus and/or a greater reduction of 3H-T binding in the striatum by high-dose TCP than by low-dose TCP may be contributing factors in the reported efficacy of the former in refractory depression.

Animals↗
PubMed1982

Effect of sequence of exposure to chlorophenols in short-term bacterial bioassays.

A bioassay using Pseudomonas fluorescens was affected by the sequence of exposure to pentachlorophenol (PCP) and 2,3,4,5-tetrachlorophenol (TCP). Surviving cells from standardized cell suspensions initially treated with PCP at concentrations ranging from 10 to 75 micrograms/ml, followed by removal of the toxicant, were not affected by a second dose of PCP at the same concentration. However, if the second dose was TCP, the test organism was sensitive to the second exposure. The most toxic sequence was an initial exposure to TCP followed by a second exposure to PCP. The response of the test organism to PCP and TCP was clearly dependent upon both the toxicant concentrations used and the sequence of toxicant addition.

Bacteria↗