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Biomedical subjects

S R Armstrong

Publications and source records attributed to S R Armstrong.

At least 19 recordsLinked to original sources
PubMed2006

The 5-HT2B antagonist and 5-HT4 agonist activities of tegaserod in the anaesthetized rat.

The 5-HT4 receptor agonist and gastroprokinetic, tegaserod, possesses 5-HT2B receptor antagonist activity. However, the relevance of such activity is unclear. In this study, the 5-HT2B receptor antagonist and 5-HT4 agonist activities of tegaserod were investigated. Two piezoelectric crystals were implanted on the stomach fundus or oesophagus of anaesthetized Sprague-Dawley rats. Measurement of the transmission time of ultrasonic pulses between the implanted crystals provided a continuous record of inter-crystal distance, and thus of muscle length. In the stomach fundus, tegaserod (1 and 3 mg kg(-1)), administered subcutaneously (s.c.), inhibited the contractile response evoked by the 5-HT2B receptor agonist, BW 723C86 (0.01-1 mg kg(-1) intravenously (i.v.)). SB 206553 (1 mg kg(-1) s.c.), a selective 5-HT2B/2C receptor antagonist, also inhibited the BW 723C86-mediated responses. In the rat oesophagus, tegaserod (0.001-0.3 mg kg(-1) i.v. or 0.003-3 mg kg(-1) s.c.) increased inter-crystal distance, consistent with smooth muscle relaxation; the responses were inhibited by the 5-HT4 antagonist, piboserod (0.1 mg kg(-1) s.c.). Data from this in vivo rat study are consistent with tegaserod-induced 5-HT4 receptor-mediated oesophageal relaxation, and antagonism of 5-HT2B receptor-mediated stomach fundus contraction. The clinical relevance of the 5-HT2B receptor antagonism of tegaserod remains to be determined.

Animals↗
PubMed2004

The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo.

1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4 receptor agonist activity. 2 Tegaserod had significant binding affinity for human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi=7.5, 8.4 and 7.0, respectively). The 5-HT2B receptor-binding affinity of tegaserod was identical to that at human recombinant 5-HT4(c) receptors (mean pKi=8.4) in human embryonic kidney-293 (HEK-293) cells stably transfected with the human 5-HT4(c) receptor. 3 Tegaserod (0.1-3 microm) inhibited 5-HT-mediated contraction of the rat isolated stomach fundus potently (pA2=8.3), consistent with 5-HT(2B) receptor antagonist activity. Tegaserod produced, with similar potency, an elevation of adenosine 3',5' cyclic monophosphate in HEK-293 cells stably transfected with the human 5-HT4(c) receptor (mean pEC50=8.6), as well as 5-HT4) receptor-mediated relaxation of the rat isolated oesophagus (mean pEC50=8.2) and contraction of the guinea-pig isolated colon (mean pEC50=8.3). 4 Following subcutaneous administration, tegaserod (0.3 or 1 mg kg(-1)) inhibited contractions of the stomach fundus in anaesthetized rats in response to intravenous dosing of alpha-methyl 5-HT (0.03 mg kg(-1)) and BW 723C86 (0.3 mg kg(-1)), selective 5-HT2B receptor agonists. At similar doses, tegaserod (1 and 3 mg kg(-1) subcutaneously) evoked a 5-HT4 receptor-mediated increase in colonic transit in conscious guinea-pigs. 5 The data from this study indicate that tegaserod antagonizes 5-HT2B receptors at concentrations similar to those that activate 5-HT4 receptors. It remains to be determined whether this 5-HT2B receptor antagonist activity of tegaserod contributes to its clinical profile.

Animals↗
PubMed2004

The timing of subsequent treatment for teeth restored with large amalgams and crowns: factors related to the need for subsequent treatment.

Crowns and large amalgams protect structurally compromised teeth to various degrees in different situations. The aim of this investigation was to evaluate the survival of teeth with these two types of restorations and the factors associated with better outcomes. Retrospective administrative and chart data were used. Survival was defined and modeled as: (1) receipt of no treatment and (2) receipt of no catastrophic treatment over five- and 10-year periods. Analyses included: Kaplan-Meier survival curves, Log-Rank tests, and Cox proportional hazards regression modeling. Crowns survived longer with no treatment and with no catastrophic treatment; however, mandibular large amalgams were least likely to have survived with no treatment, and maxillary large amalgams were least likely to have survived with no catastrophic treatment. Having no adjacent teeth also decreased survival. Crowns survived longer than large amalgams, but factors such as arch type and the presence of adjacent teeth contributed to the survival of large amalgams.

Bicuspid↗
PubMed2003

Effect of smear layer on root demineralization adjacent to resin-modified glass ionomer.

The cariostatic effect of resin-modified glass ionomer (RMGI) on secondary root caries is well-documented. However, this beneficial effect may be dependent upon the mode of cavity surface treatment. To investigate this relationship, we studied 4 cavity surface treatments prior to the placement of RMGI: no treatment (None), polyacrylic acid (PAA), phosphoric acid (H(3)PO(4)), and Scotchbond Multi-Purpose adhesive (SMP) as a control. Specimens were aged for two weeks in synthetic saliva, thermocycled, and subjected to an artificial caries challenge (pH 4.4). Polarized light microscopy (PLM) and microradiography (MRG) showed significantly less demineralization with the H(3)PO(4) cavity surface treatment as revealed by ANOVA and Tukey's multiple comparisons (p < or = 0.05). Dentin fluoride profiles determined by electron probe microanalysis (EPMA) supported PLM and MRG findings. It may be concluded that removal of the smear layer with phosphoric acid provides significantly enhanced resistance to secondary root caries formation adjacent to RMGI restorations.

Acid Etching, Dental↗
PubMed2001

Mode of failure in the dentin-adhesive resin-resin composite bonded joint as determined by strength-based (muTBS) and fracture-based (CNSB) mechanical testing.

OBJECTIVE: To determine the failure mode between dentin-adhesive resin-resin composite bonded joint produced with a chevron-notch short-bar (CNSB) and microtensile test methods. METHODS: Forty teeth were randomly selected for microtensile and forty for CNSB specimen fabrication and stored in 0.5% chloramine T at 37 degrees C until respective static load to failure testing at 30 and 180days. Failure modes were categorized by SEM and tested with Fisher's exact test. Within respective mechanical testing methods the probability of failure curve distributions being significantly different were analyzed by the Wald chi-square statistic. RESULTS: The characteristic fracture toughness at 30- and 180-day storage was 0.82 and 0.87MPam(1/2), while the Weibull Modulus (m) for the failure distributions, was 4.60 and 4.56, respectively. No significant difference was demonstrated in the failure distributions between these groups (p=0.45). The characteristic tensile strength (muTBS(o)) at 30- and 180-day storage was 52.53 and 14.71MPa with an m of 3.04 and 1.56, respectively. Failure distributions for muTBS groups were significantly different (p<0.001). K(IvM) failure modes, regardless of storage time, were within the adhesive joint with 30-day debonds primarily through the top region of the hybrid layer (THL) and after 180-days involving the bottom of the hybrid layer (BHL). The 30-day muTBS group demonstrated a propensity to debond in dentin or resin composite substrates but after 180-days storage debonds again involved the BHL. SIGNIFICANCE: The weak links in the dentin-adhesive resin-resin composite bonded joint may be the interphase regions between the THL and the adhesive resin and the BHL and dentin.

Adhesiveness↗
PubMed2001

The influence of water storage and C-factor on the dentin-resin composite microtensile bond strength and debond pathway utilizing a filled and unfilled adhesive resin.

OBJECTIVE: To test the elastic wall concept utilizing adhesive resins of varying stiffness in a low- and high-C-factor cavity design after short- and long-term water storage. METHODS: A flat and box-shaped cavity was restored on occlusal dentin with a resin composite using a filled and unfilled adhesive resin from which microtensile specimens with a 0.5mm(2) cross-sectional area were formed. After storage for 30- and 150-days the microtensile bond strength (muTBS) was determined in a Zwick materials testing machine and the subsequent debond pathway was examined under scanning electron microscopy. Fisher's exact test was used to determine differences in joint and substrate failure modes and a Weibull regression model with gamma frailties was used to test for differences between failure distributions. Tests for three-way and two-way interactions were also completed for storage time, C-factor and adhesive. All tests were at 95% confidence levels. RESULTS: The characteristic strength (TBS degrees ) for the Optibond FL adhesive applied on a flat cavity was 47.57 and 20.90MPa and a box-shaped cavity was 49.26 and 17.49MPa for short- and long-term storage, respectively, while the corresponding TBS degrees for the unfilled Optibond adhesive on the flat cavity design was 36.93 and 32.68MPa and in a box-shaped cavity was 32.84 and 15.46MPa. Combining all groups according to storage time revealed a three-fold increase in the debond pathway including the bottom of the hybrid layer. SIGNIFICANCE: Evidence suggests that the durability of the bonded joint is threatened by hydrolysis and the most susceptible region is the bottom half of the hybrid layer and in low C-factor cavity designs a more flexible adhesive resin liner was more durable.

Adhesiveness↗
PubMed2001

Association between microtensile bond strength and leakage in the indirect resin composite/dentin adhesively bonded joint.

PURPOSE: Develop a methodology to correlate microtensile bond strength (microTBS) and leakage within the same site of a specimen and evaluate the predominate debond and leakage pathways. MATERIALS AND METHODS: A Class II (MO) slot cavity was prepared in 37 extracted human molars and restored with indirect resin composite restorations. The restored teeth were thermocycled 300X between 5 and 55 degrees C and then stained with silver. Two specimens per tooth were obtained by diamond saw sectioning for measurement of leakage (microm) and microtensile bond strength (MPa) at the gingival wall and then tested for association with regression analysis. Scanning electron microscopy techniques and energy dispersive spectroscopy (EDS) were used to evaluate the debond and leakage pathways. RESULTS: Association between leakage and bond strength was not significant (t=1.31, p=0.198). All 74 samples debonded within the joint, predominantly at the hybrid layer-adhesive resin region with only one specimen including a small portion of resin cement in the debond pathway. Secondary and backscatter imaging and EDS analysis showed leakage in all samples that involved the hybrid layer. CONCLUSION: This study demonstrates a feasible method for evaluating leakage and bond strength at the joint interface within the same specimen.

Composite Resins↗
PubMed1998

Microtensile bond strength testing and failure analysis of two dentin adhesives.

OBJECTIVES: This investigation was conducted to determine the tensile bond strength of two dental adhesive using a recently introduced "microtensile" bond strength testing design and to verify the failure mode for each test specimen with scanning electron microscopy (SEM). METHODS: Extracted human molars were mounted in stone and the enamel was removed the occlusal surface perpendicular to the long axis of the tooth. A composite resin crown was formed on this flat dentin surface utilizing each dental adhesive system according to manufacturer's instructions. Twenty-four hours later the bonded test specimens were sectioned perpendicular to the adhesive joint, producing six to seven thin slabs per tooth. These dentin/adhesive/composite resin slabs were sectioned free from the stone block and mounted into custom Plexiglas fixtures for trimming and subsequent tensile bond strength testing at 7 d post-bonding. The bond strength of the two adhesives was statistically compared with the t test. The broken specimens were examined with SEM to determine the fracture location or failure mode. Failures for each adhesive system were categorized as either interfacial (joint or mixed) or substrate (dentin and composite) and evaluated by Fisher's exact test. RESULTS: The tensile bond strength and failure modes of All-Bond 2 (Bisco) and Optibond FL (Kerr) were not significantly different. Sixty per cent (12/20) of fractures involving All Bond 2 occurred at the interface, with seven being entirely maintained within the joint, whereas Optibond FL had 35% (7/20) involving some portion of the interface, two totally within the joint. Cohesive fractures of either dentin or composite accounted for 55% of the total failure modes (21/40). The remaining dentin thickness did not affect the measured tensile bond strength. SIGNIFICANCE: This versatile new method permits multiple measurements from a single tooth or small surface areas within a restoration but careful interpretation of the failure mode is required to prevent inappropriate conclusions about the utility of the test.

Crowns↗
PubMed1998

Effect of hybrid layer on fracture toughness of adhesively bonded dentin-resin composite joint.

OBJECTIVES: Micromechanical retention from the hybrid layer is generally believed to be the mechanism of adhesion of current generation dentin bonding agents. The purpose of this investigation is to evaluate the interfacial fracture toughness of a commercial dentin bonding agent with and without this hybrid layer. METHODS: Ten extracted molars (AB2) were flattened on the occlusal surface, All-Bond 2 Universal Adhesive System (Bisco) was applied according to manufacturer's directions and a resin composite (Prodigy, Kerr) crown was formed. Another group of ten molars (AB2Cl) was handled identically with the exception of a 1 min gentle scrubbing application of 5.25% sodium hypochlorite after acid etching to remove the acid-exposed collagen. Plane-strain chevron-notch short bar fracture toughness specimens were fabricated from all 20 composite crowns and tested according to ASTM E1304-89. Each group was tested to failure in tensile mode at 0.1 mm min-1 and the maximum load at failure was used to determine plane-strain fracture toughness (KQvM). Weibull parameters were calculated and fracture probability distributions were tested for significant difference at the 95% confidence level. Scanning electron microscopy was employed on broken specimens (18/20) to describe the failure mode. RESULTS: Weibull distributions were not significantly different with characteristic plane-strain fracture toughness from maximum load (KQvM0) of 0.97 MPa m1/2 and 0.81 MPa m1/2 and a Weibull modulus of 4.7 and 3.9, respectively, for AB2 and AB2Cl. All AB2 samples failed within the adhesive joint, while the AB2Cl crack propagated from the interphase of adhesive resin and dentin to 1-2 microns into dentin. SIGNIFICANCE: Under the conditions of this study, the presence of collagen did not contribute to a significantly stronger bonded joint. Interfacial fracture toughness evaluation of the dentin-resin composite bimaterial interface shows promise for future investigations.

Collagen↗
PubMed1996

Active site amino acids that participate in the catalytic mechanism of nucleoside 2'-deoxyribosyltransferase.

The importance of eight nucleoside 2'-deoxyribosyltransferase residues for catalysis was investigated by site-directed mutagenesis. Each residue was selected because of its proximity to nucleophile Glu-98 or on its potential contribution to intrinsic protein fluorescence. Mutation of Asp-72, Asp-92, Tyr-7, Trp-12, and Met-125 resulted in over a 90% activity loss whereas mutation of Tyr-157, Trp-64, and Trp-127 produced less than a 80% activity loss. The magnitude of the perturbation on catalysis by mutation, however, was dependent on donor substrate. The kcat values for dIno hydrolysis by these mutants were greater than 25% of that for native enzyme. Although mutant and native enzymes bound substrate analogues with comparable affinities, Km values for dIno hydrolysis varied over a 1000-fold range. The pH dependence of Glu-98 esterification by dCyd suggested that amino acids with pK values of 4.2 and 7.5 were relevant for catalysis. The intrinsic protein fluorescence was attributed primarily to Trp-127 (approximately 80%). Pre-steady-state kinetic parameters for deoxyribosylation of mutant enzymes by dCyd, dThd, and dAdo were determined by monitoring changes in enzyme fluorescence. Collectively, results from mutagenesis suggest that, depending upon substrate, either Asp-92 or Asp-72 functions as the general acid catalyst, and that this enzyme undergoes a change in conformation upon Glu-98 deoxyribosylation.

Binding Sites↗
PubMed1996

Crystal structures of nucleoside 2-deoxyribosyltransferase in native and ligand-bound forms reveal architecture of the active site.

BACKGROUND: Nucleoside 2-deoxyribosyltransferase plays an important role in the salvage pathway of nucleotide metabolism in certain organisms, catalyzing the cleavage of beta-2'-deoxyribonucleosides and the subsequent transfer of the deoxyribosyl moiety to an acceptor purine or pyrimidine base. The kinetics describe a ping-pong-bi-bi pathway involving the formation of a covalent enzyme-deoxyribose intermediate. The enzyme is produced by a limited number of microorganisms and its functions have been exploited in its use as a biocatalyst to synthesize nucleoside analogs of therapeutic interest. RESULTS: We describe the crystal structure of the enzyme with and without bound ligand. The native structure was solved by the single isomorphous replacement with anomalous scattering method (SIRAS) and refined to 2.5 A resolution resulting in a crystallographic R factor of 16.6%. The enzyme comprises a single domain that belongs to the general class of doubly-wound alpha/beta proteins; it also exhibits a unique nucleoside-binding motif. X-ray analysis of enzyme-purine and enzyme-pyrimidine complexes presented here reveals that the active site lies in a cleft formed by the edge of the beta sheet and two alpha helices and contains side chains from two subunits. CONCLUSIONS: These results indicate residues that may be important in substrate binding and catalysis and thus may serve as a framework for elucidating the mechanism of enzyme activity. In particular, the proposed nucleophile, Glu98, lies in the nucleoside-binding pocket at an appropriate position for nucleophilic attack. A comparison of the enzyme interactions with both a purine and pyrimidine ligand provides some insight into the structural basis for enzyme specificity.

Binding Sites↗
PubMed1985

Restoration of Class IV and VI defects in anterior teeth with an unfilled resin.

The etched resin technique with unfilled acrylic resin has been successful for Class IV and VI defects on anterior incisor teeth and has proven more useful than alternatives in the immediate treatment of traumatized teeth. The advantages of this approach are ease of operation, excellent retention, conservative tooth preparation, excellent esthetics, lower cost to patient, reduced additional insult to recently traumatized teeth in stabilizing them, stable color, and lack of trauma to opposing teeth (Fig. 10).

Acrylic Resins↗