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PubMed1980

The effects of phencyclidine and three analogues on motor performance in mice.

A measure of motor impairment in which mice were required to climb to the top of an inverted screen was used to study the effects of phencyclidine. The time course of effects of phencyclidine after intravenous, intraperitoneal and per os administrations was compared. The intravenous route resulted in a rapid peak effect of activity and phencyclidine was most potent by this route. Peak effects of phencyclidine were seen by 30 min after intraperitoneal and per os administrations and the decline in activity was not very different with these two routes. However, greater peak effects were seen with intraperitoneal than per os administration. The effects of phencyclidine were also compared to ketamine, N-ethyl-phenylcyclohexylamine (PCE) and 1-[1-(2-thienyl)-cyclohexyl]-piperidine (TCP). The order of potency was PCE greater than phencyclidine greater than TCP greater than ketamine. PCE, phencyclidine and TCP had similar time courses of activity, whereas ketamine was shorter acting.

Animals↗
PubMed1988

Bactericidal efficacy of metronidazole against bacteria of human carious dentin in vitro.

The bactericidal efficacy of metronidazole against bacteria in carious dentin was clarified by measuring (1) the difference between bacterial recovery from suspensions of carious dentin on metronidazole-containing BHI-Blood agar plates (10 micrograms/ml) and control plates and (2) the difference between bacterial recovery from carious lesions of freshly extracted teeth, covered by alpha-tricalcium phosphate (TCP) cement containing metronidazole (5%) for 1-3 days and that covered by TCP only. More than 10(3) bacteria per milligram sample were recovered from carious dentin. More than 99% of the bacteria were, however, not recovered when samples were inoculated on metronidazole-containing BHI-Blood agar plates or when the lesions were covered by TCP cement containing metronidazole, indicating that metronidazole effectively disinfected the carious dentin.

Bacteria↗
PubMed1989

Bactericidal efficacy of metronidazole against bacteria of human carious dentin in vivo.

The bactericidal efficacy of metronidazole (MN) against bacteria of carious dentin was estimated by measuring bacterial recovery with or without application of MN to dentinal lesions in vivo. More than 10(3) colony-forming units of bacteria per milligram of sample were recovered from the samples of carious dentin. However, none were recovered from the samples of dentinal lesions which had been covered by alpha-tricalcium phosphate (TCP) cement containing MN in situ for 1 day, 1 month, 1 year and/or 2 years in vivo. Placebo experiments in which carious dentin was covered by TCP cement without MN showed that TCP itself was not bactericidal. Bactericidal efficacy of MN in situ is clearly demonstrated, indicating that MN is a valuable material in caries treatment to disinfect carious dentin.

Adolescent↗
PubMed2005

Neuroprotective properties of the natural vitamin E alpha-tocotrienol.

BACKGROUND AND PURPOSE: The current work is based on our previous finding that in neuronal cells, nmol/L concentrations of alpha-tocotrienol (TCT), but not alpha-tocopherol (TCP), blocked glutamate-induced death by suppressing early activation of c-Src kinase and 12-lipoxygenase. METHODS: The single neuron microinjection technique was used to compare the neuroprotective effects of TCT with that of the more widely known TCP. Stroke-dependent brain tissue damage was studied in 12-Lox-deficient mice and spontaneously hypertensive rats orally supplemented with TCT. RESULTS: Subattomole quantity of TCT, but not TCP, protected neurons from glutamate challenge. Pharmacological as well as genetic approaches revealed that 12-Lox is rapidly tyrosine phosphorylated in the glutamate-challenged neuron and that this phosphorylation is catalyzed by c-Src. 12-Lox-deficient mice were more resistant to stroke-induced brain injury than their wild-type controls. Oral supplementation of TCT to spontaneously hypertensive rats led to increased TCT levels in the brain. TCT-supplemented rats showed more protection against stroke-induced injury compared with matched controls. Such protection was associated with lower c-Src activation and 12-Lox phosphorylation at the stroke site. CONCLUSIONS: The natural vitamin E, TCT, acts on key molecular checkpoints to protect against glutamate- and stroke-induced neurodegeneration.

Animals↗
PubMed2006

In vivo performance of biodegradable calcium phosphate glass ceramics using the rabbit model: histological and SEM observation.

Two MK5 (45CaO-45P(2)O(5)-5MgO-5K(2)O, in mol%) and MT13 (45CaO-37P(2)O(5)-5MgO-13TiO(2), in mol%) glasses are prepared in the meta- and pyrophosphate regions and crystallized to obtain MK5B and MT13B, respectively. MK5B was obtained by controlled crystallization, and MT13B by powder sintering. As a result of these heat treatment processes, the crystalline phases precipitated in the glassy matrix are KCa(PO(3))(3), beta-Ca(PO(3))(2), beta-Ca(2)P(2)O(7) and Ca(4)P(6)O(19) phases for MK5B and CaTi(4)(PO(4))(6), TiP(2)O(7), alpha- and beta-Ca(2)P(2)O(7) phases for MT13B. To assess the in vivo biological behavior of these glass ceramics, a mixed granulometry in the range 250-355 mum and 355-425 mum with a ratio of 1/1 was implanted for 2, 4, and 12 weeks in the tibiae of Japanese white rabbits. The results showed that the in vivo behavior was strongly affected by their solubility. All implanted materials, MK5B and MT13B, and beta-tricalcium phosphate (beta-TCP) as control material, showed signs of degradation in vivo. However, the levels of degradation were quite different throughout the implantation periods. The highest degradation was observed for MK5B glass ceramic and the lowest for MT13B with beta-TCP in-between. All implanted materials allow for new bone formation in the bone defect area. At the longest implantation period (12 weeks), the MT13B and beta-TCP materials were almost completely surrounded by new bone tissue, whereas MK5B showed some unfilled spaces. This behavior is discussed in terms of the high degradation observed in previous studies.

Absorbable Implants↗
PubMed2004

CUPULIFORMIS establishes lateral organ boundaries in Antirrhinum.

Cupuliformis mutants are defective in shoot apical meristem formation, but cup plants overcome this early barrier to development to reach maturity. CUP encodes a NAC-domain transcription factor, homologous to the Petunia NAM and Arabidopsis CUC proteins. The phenotype of cup mutants differs from those of nam and cuc1 cuc2 in that dramatic organ fusion is observed throughout development. In addition to cotyledon and floral organ fusions, severe lateral organ fusion is found in leaves and inflorescences, and the apical meristem becomes highly fasciated. These features reveal a role for CUP in the establishment of all above ground organ boundaries. Consistent with this function, CUP is expressed at the boundaries of all lateral organs and meristems. It is not currently known how NAC-domain genes act to establish organ boundaries. Here, we show that CUP directly interacts with a TCP-domain transcription factor. Members of the TCP-domain family have previously been shown to regulate organ outgrowth. Our results suggest a model for the establishment of organ boundaries based on the localised expression of NAC-domain and TCP-domain factors.

Antirrhinum↗
PubMed1977

Effect of pretreatment with tricresylphosphates and phenobarbital on the metabolism and toxicity of procaine in rats.

We examined the effects of pretreatment with phenobarbital and tricresylphosphates, TOCP and TCP, on the metabolism and toxicity of procaine in rats. A single administration of procaine at a dose of 250 mg/kg intraperitoneally to adult rats caused convulsion, however, phenobarbital (80 mg/kg intraperitoneally daily, 4 days) pretreatment protected against the toxicity or procaine. In contrast, pretreatment of rats with TOCP (10 mg/kg per os) or TCP (10 mg/kg per os) revealed a higher incidence of toxicity as compared to control rats. Mortality in procaine-treated rats was significantly decreased with phenobarbital-pretreatment and, conversely, increased with TOCP and TCP. Paralysis, convulsion and death were induced at the brain level of procaine of 0.303 +/- 0.025, 0.480 +/- 0.026 and 0.565 +/- 0.018 mumole/g brain wet weight, respectively. Toxic effects of procaine were, therefore, concluded to be due to the accumulation of the drug in the brain.

4-Aminobenzoic Acid↗
PubMedDate not supplied

Long-term desipramine or chlorpromazine treatment and rat brain N-methyl-D-aspartate receptor.

The effects of tricyclic antidepressants and antipsychotic drugs on the NMDA receptor in rat brain were investigated. Both types of drugs, in the micromolar concentration range and with Hill coefficients greater than unity, inhibited the binding of [3H]TCP to rat brain membranes. Tricyclic antidepressants containing secondary amine on the aliphatic side chain were more potent than the corresponding tertiary amine derivatives. Antipsychotic drugs containing large side chains were much less active than chlorpromazine. Neither tricyclic antidepressants nor antipsychotic drugs had an inhibitory effect on [3H]CPP binding to the glutamate site of the NMDA complex. Chronic administration of desipramine or chlorpromazine did not change the binding parameters of [3H]TCP to rat cerebral cortex membranes. It is possible that these psychoactive drugs bind to a site adjacent to the [3H]TCP binding site within the ionic channel of the NMDA receptor complex.

Animals↗
PubMed1998

Fertilization promoting peptide: an important regulator of sperm function in vivo?

Fertilization promoting peptide (FPP; pGlu-Glu-ProNH2), a tripeptide structurally related to thyrotrophin releasing hormone, is produced by the prostate gland and released into seminal plasma. Recent studies carried out in vitro have revealed that FPP elicits biologically important responses in both mouse and human spermatozoa. In the presence of physiological concentrations of FPP (50-100 nmol l(-1)), uncapacitated spermatozoa undergo accelerated capacitation and so become potentially fertilizing more quickly, while capacitated spermatozoa are inhibited from undergoing spontaneous acrosomal exocytosis, an event that would make them non-fertilizing. In vivo, these responses would be very important since relatively few spermatozoa reach the site of fertilization; FPP could help to ensure that these were potentially fertilizing cells. A putative receptor (TCP-11) for FPP has been identified in mice. The gene for TCP-11 (which has a human homologue) maps to the t-complex, a region known to contain genes affecting male fertility. Current evidence indicates that FPP and TCP-11 act by modulating the activity of adenylyl cyclase and hence production of cAMP, a signal transduction pathway shown to be important in the acquisition of fertilizing ability. These results suggest that FPP plays an important role in normal fertility and that insufficient FPP could reduce fertility. Prostatic dysfunction can lead to decreased synthesis of FPP and increased synthesis of FPP-related peptides with reduced biological activity, both of which could compromise fertility in vivo. Given that 'male factor' infertility is a common contributor to subfertility in couples, it may prove possible to develop new therapeutic treatments, for at least some males, using FPP. In addition, this ligand-receptor pair could provide a novel target for male contraception.

Animals↗
PubMed1985

An evaluation of tricalcium phosphate implants in human periodontal osseous defects of two patients.

This study evaluated the use of tricalcium phosphate (TCP) ceramic implant material in periodontal osseous defects. Thirteen defects in two patients were treated with mucoperiosteal flaps and placement of TCP. The defects were evaluated clinically and radiographically utilizing standardized probe placement and radiographic technique. Clinically, there was a mean probing pocket reduction of 4.5 mm as a result of a mean gain of clinical probing attachment level of 2.0 mm and a mean gingival recession of 2.5 mm. Radiographically, there was a mean "fill" of 1.8 mm. Six teeth were removed by block biopsy for histologic analysis, three at 3 months, one at 6 months and two a 9 months. The TCP particles were well tolerated and encapsulated by fibrous connective tissue, but the particles did not stimulate new bone growth. The junctional epithelium ended 1.62 mm coronal to the apical extent of a reference notch placed at the base of the defect. Although new cementum was observed, there was limited evidence of new attachment.

Adult↗
PubMed1986

Bioceramic implants in surgical periodontal defects. A comparison study.

The healing response of two commercially available bioceramics, beta tricalcium phosphate (TCP) and hydroxylapatite (HA), was compared after implantation in surgically created defects in dogs. Three 18 to 24 month old female Labrador dogs were used. Under general anesthesia 3-wall defects were created on the canines and premolars. The roots were planed, and reference notches were placed to identify the alveolar crest and the apical extent of the defects. TCP or HA was placed in alternating canine defects. The premolars received no implants and served as controls. Plaque management was accomplished by biweekly brushing with 0.2% chlorhexidine. Following healing periods of 5, 12 and 16 weeks, the dogs were sacrificed and perfused with 10% formalin. Six-mu step serial sections were evaluated by light microscopy. Healing against the root planed surface varied from a long junctional epithelium to a connective tissue reattachment in new cementum. TCP particles were actively resorbed by giant cells and macrophages and were incorporated into new bone matrix. The HA particles were encapsulated by fibrous connective tissue and rarely seen in contact with repairing bone. Bone formation was slower around HA particles at all time periods. Some evidence of HA particle resorption was seen at each time period.

Alveolar Process↗
PubMed1988

The effect of supracrestal tricalcium phosphate ceramic-microfibrillar collagen grafting on postsurgical soft tissue levels.

In this clinical study, a combined tricalcium phosphate ceramic (TCP) microfibrillar collagen supracrestal graft was used in conjunction with pocket elimination surgery as a soft tissue space filler to maintain marginal and interproximal tissue heights. Fifteen volunteer adult patients (8 male, 7 female) aged 37 to 48 years were selected. Standardized clinical probing measurements were used to evaluate soft tissue recession, clinical attachment, and probing pocket depths. Intraoral photographs and radiographs supplemented documentation. Twenty-five paired test and control sites were evaluated. Following flap surgery and minor osteoplasty, test defects received supracrestal grafts of TCP microfibrillar collagen prior to flap closure. Intrabony defects were excluded. Treatment modalities were compared by analyzing changes in clinical probing measurements over four months using the students t test for paired samples at the 0.01 level of significance. Supracrestal grafting resulted in 16.74% less soft tissue recession than the control sites. In addition, there was a significant gain in clinical attachment levels compared with the controls. All implanted sites demonstrated an advantage in the use of supracrestal TCP-collagen grafts compared with the controls. This treatment modality may have value in reducing esthetic deformities, food impaction areas, and root exposure that often occur following periodontal surgery.

Adult↗
PubMed1990

Bone formation in tricalcium phosphate-filled periodontal intrabony lesions. Histological observations in humans.

The capacity of a tricalcium phosphate (TCP) ceramic to promote bone formation after grafting in intrabony defects was studied in humans. Five biopsies were collected from 4 patients during reentry surgery 16 to 40 months after implantation. They were processed without demineralization for histological examination. In the less mature samples, the grafted material was surrounded by a highly fibrous, highly cellular, and poorly vascularized connective tissue. Howship's lacuna-like cavities were clearly visible at the surface of the material. They contained resorbing mononuclear phagocytes. At a more mature stage, TCP granules were embedded in an acellular fibrous material which underwent mineralization from the medullary spaces towards the granules. The bone formed was subsequently remodeled. The implanted material itself was progressively modified. It first acquired the staining appearance of bone. After its structure became loose and vacuolated, it was invaded by cells and vessels. The present data indicate that TCP has osteogenic potential and is subject to degradation. Unlike in experimental wounds, these processes are of long duration in human defects.

Adult↗
PubMed2005

Clinical evaluation of an enamel matrix protein derivative combined with either a natural bone mineral or beta-tricalcium phosphate.

BACKGROUND: The purpose of the present study was to compare the healing of deep intrabony defects following treatment with an enamel matrix protein derivative (EMD) combined with either a natural bone mineral (NBM) or beta-tricalcium phosphate (beta-TCP). METHODS: Twenty-four patients with advanced periodontal disease, each of whom displayed one intrabony defect, were randomly treated with a combination of either EMD + NBM or EMD + beta-TCP. Clinical evaluation was performed at baseline and 1 year following therapy. RESULTS: No differences in any of the investigated parameters were observed at baseline between the two groups. Healing was uneventful in all patients. At 1 year after therapy, the sites treated with EMD + NBM showed a reduction in mean probing depth (PD) from 7.9 +/- 1.0 mm to 3.2 +/- 0.6 mm and a change in mean clinical attachment level (CAL) from 8.8 +/- 1.1 mm to 4.5 +/- 0.6 mm (P < 0.001). In the group treated with EMD + beta-TCP, the mean PD was reduced from 7.8 +/- 1.2 mm to 3.2 +/- 0.9 mm, and the mean CAL changed from 8.8 +/- 1.2 mm to 4.7 +/- 1.2 mm (P < 0.001). In both groups, all sites gained at least 3 mm of CAL. CAL gains of 4 or 5 mm were measured in the majority of the cases (75%), irrespective of treatment modality. No statistically significant differences in terms of PD reductions and CAL gains were observed between the two groups. CONCLUSION: Within the limits of the present study, both therapies resulted in significant PD reductions and CAL gains 1 year after surgery.

Adult↗
PubMed2006

Superior effect of MD05, beta-tricalcium phosphate coated with recombinant human growth/differentiation factor-5, compared to conventional bone substitutes in the rat calvarial defect model.

BACKGROUND: MD05 consists of beta-tricalcium phosphate (beta-TCP) coated with recombinant human growth/differentiation factor-5 (rhGDF-5) and is under evaluation as an osteoinductive and osteoconductive bone graft material for use in dental and maxillofacial applications. The objective of this study was to compare the bone regenerative properties of MD05 with those of conventional commercially available bone substitutes. METHODS: Full-thickness, 6-mm diameter, calvarial critical-size defects (two per animal) were created in adult Sprague-Dawley rats. Groups of rats were implanted with the following: 1) MD05; 2) bovine bone mineral; 3) bovine bone mineral with collagen; 4) bovine bone mineral with synthetic peptide, 5) beta-TCP (from two different manufacturers); or 6) no filling material (sham controls). Blinded macroscopic analysis, histopathologic analysis, and histomorphometric analysis were carried out 6 weeks after implantation. RESULTS: New bone formation assessed histomorphometrically was about five times greater with MD05 than with the other bone substitutes tested, and bone repair was well advanced in MD05-filled defects after 6 weeks. The extent of fibrous tissue and residual implant were significantly lower in the MD05 group. In contrast to the other materials, the use of MD05 was associated with the complete osseous bridging of the defect and with the presence of normal bone marrow. The osteoinductive effect of rhGDF-5 was apparent from the more pronounced bone ingrowth observed with MD05 compared to the beta-TCP carrier alone. All implants showed good biocompatibility. CONCLUSION: MD05 achieved superior bone regeneration compared to conventional materials and is a promising new bone substitute for dental and maxillofacial applications.

Animals↗
PubMed1997

Effect of nitric oxide, prostacyclin, and thromboxane on the vasospastic action of hydrogen peroxide on human umbilical artery.

BACKGROUND: The effect of hydrogen peroxide (H2O2) on vascular tone in the human umbilical artery was investigated to determine the mechanism of vasospasm in preeclampsia. METHODS: Helical sections of the umbilical artery were obtained from healthy pregnant women who delivered between the 37th and 39th week of gestation. Changes in the maximal tension induced by prostaglandin F2 alpha (PG F2 alpha) were measured (isometric mechanical activity). Segments were treated with H2O2 alone or H2O2 after pretreatment with a scavenger of hydroxyl radicals (mannitol), an inhibitor of thromboxane synthesis (sodium ozagrel), and an inhibitor of nitric oxide synthesis (L-NG-monomethyl arginine, LNMA), or an inhibitor of prostacyclin synthesis (tranylcypromine, TCP). RESULTS: Vascular tension was potentiated by H2O2 in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of H2O2. Removal of the endothelium decreased the vascular tension induced by H2O2. Treatment with TCP and LNMA potentiated the vascular tension. Pretreatment with TCP and LNMA reduced the vasospastic action of H2O2, whereas pretreatment with sodium ozagrel did not. CONCLUSION: Vascular tension in human umbilical arteries was potentiated by H2O2, and may be mediated by a suppression of the activity of nitric oxide or of prostacyclin. A direct action of H2O2 on vascular smooth muscle may also be involved.

Epoprostenol↗
PubMed1990

Contrasting effects of norepinephrine and 5-hydroxytryptamine on contractility of abdominal aorta of two kidney-two clip hypertensive rats. Effects of inhibitors of arachidonic acid metabolic enzymes.

This study intends to: 1) define reactivity in vessels of two kidney-two clip (2K2C) hypertensive rats (6-11 days after clipping); 2) determine the possible involvement of prostaglandins in modulating contractile vascular responses. Cumulative dose-response curves to norepinephrine (NE), 5-hydroxytryptamine (5-HT) and potassium chloride (KCl) were elicited on helical strips of abdominal aorta both in the absence and in the presence of prostacyclin synthetase (transylcypromine, TCP, 0.25mM) or cyclooxygenase (indomethacin, IND, 0.014 mM and acetylsalicylic acid, ASA, 0.20 mM) inhibitors Vessels of hypertensive animals developed significantly less tension to NE (n = 21) but higher tension and lower ED50 in response to 5-HT (n = 9) than sham control rat vessels. Force development to KCl (n = 9) was not statistically different between hypertensive and sham vessels. Vascular responses were decreased with the inhibitors, but the contrasting effects of NE and 5-HT on clip vessels were maintained. Threshold doses of PGE2 significantly reversed the effect of IND but not that of TCP on NE responses. Threshold doses of PGI2 had no significant effect on NE and 5-HT responses under TCP. The results would indicate: 1) different functional alterations for contractions to NE and 5-HT appear to have developed in vessels of 2K2C hypertensive rats; 2) PGE2 effectively contributes to modulation of NE responses in rat aorta strips; 3) these experiments suggest that prostaglandins do not play a significant role in the altered contractility of vessels in hypertensive rats.

Animals↗
PubMed2002

Beta-tricalcium phosphate as a substitute for autograft in interbody fusion cages in the canine lumbar spine.

OBJECT: An interbody fusion cage has been introduced for cervical anterior interbody fusion. Autogenetic bone is packed into the cage to increase the rate of union between adjacent vertebral bodies. Thus, donor site-related complications can still occur. In this study a synthetic ceramic, beta-tricalcium phosphate (TCP), was examined as a substitute for autograft bone in a canine lumbar spine model. METHODS: In 12 dogs L-1 to L-4 vertebrae were exposed via a posterolateral approach, and discectomy and placement of interbody fusion cages were performed at two intervertebral disc spaces. One cage was filled with autograft (Group A) and the other with TCP (Group B). The lumbar spine was excised at 16 weeks postsurgery, and biomechanical, microradiographic, and histological examinations were performed. Both the microradiographic and histological examinations revealed that fusion occurred in five (41.7%) of 12 operations performed in Group A and in six (50%) of 12 operations performed in Group B. The mean percentage of trabecular bone area in the cages was 54.6% in Group A and 53.8% in Group B. There were no significant intergroup differences in functional unit stiffness. CONCLUSIONS: Good histological and biomechanical results were obtained for TCP-filled interbody fusion cages. The results were comparable with those obtained using autograft-filled cages, suggesting that there is no need to harvest iliac bone or to use allo- or xenografts to increase the interlocking strength between the cage and vertebral bone to achieve anterior cervical interbody fusion.

Animals↗