Biomedical subjects

L J Wallace

Publications and source records attributed to L J Wallace.

At least 37 records · Page 2Linked to original sources

PubMed1997

Differential effect of sensitizing regimen on induction of Fos-protein and locomotor activity elicited by apomorphine in rats.

At doses that elicit behavioral activation, apomorphine does not induce Fos-protein in the nucleus accumbens of control animals but does under conditions of denervation supersensitivity. The purpose of this study was to determine whether apomorphine induces Fos-protein in animals sensitized by repeated treatment with apomorphine and whether the magnitude of such induction parallels the magnitude of behavioral response observed after different sensitizing paradigms. Apomorphine did induce Fos-protein expression in animals pretreated with apomorphine; however, the rats showing highest levels of induction were not those showing the largest behavioral responses.

Animals↗

PubMed1997

Association between pelvic muscle mass and canine hip dysplasia.

OBJECTIVE: To investigate the relationship between pelvic muscle mass and development and expression of canine hip dysplasia (CHD). DESIGN: Prospective study. ANIMALS: 5 Greyhounds with anatomically normal hip joints, 59 German Shepherd Dogs (23 with CHD, 24 with near-normal hip joints, and 12 with normal hip joints), and 18 German Shepherd Dog-Greyhound crossbreeds (7 with CHD, 6 with near-normal hip joints, and 5 with normal hip joints) between 12 and 47 months old in which pelvic muscle mass was evaluated. Pectineal muscle and hip joint development were evaluated in 25 German Shepherd Dogs at 8 and 16 or 24 weeks of age. PROCEDURES: For evaluation of pelvic muscle mass, individual pelvic muscles were weighed and hip joints were assigned a score on the basis of severity of degenerative changes. For evaluation of pectineal muscle development, muscle sections were stained and examined. RESULTS: Pelvic muscle mass was greatest in Greyhounds, intermediate in crossbred dogs, and smallest in German Shepherd Dogs. Differences in pelvic muscle mass among breeds were attributable to differences in weights of individual muscles. Hip score was negatively correlated with pelvic muscle mass and weights of selected pelvic muscles. Dogs with pectineal hypotrophy at 8 weeks of age had type-2 muscle fiber paucity or muscle fiber-type grouping at 16 or 24 weeks of age. At 8 weeks of age, hip joints were composed of multiple centers of ossification, and the acetabulum was largely cartilaginous. By 24 weeks of age, the pelvic bones were largely, although incompletely, fused. CLINICAL IMPLICATIONS: Diminished pelvic muscle mass in dogs with CHD and altered muscle fiber size and composition in 8-week-old dogs that subsequently develop CHD strongly suggest that abnormalities of pelvic musculature are associated with development of CHD. The complex development of the hip joint from multiple centers of ossification may make the joint susceptible to abnormal modeling forces that would result from abnormalities in pelvic muscle mass.

Animals↗

PubMed1997

Enhancement of the locomotor response to apomorphine in pertussis toxin-treated animals depends on the site of pertussis toxin injection into the ventral tegmental area.

The locomotor stimulant response to either systemic or intra-accumbens amphetamine was enhanced 1-2 weeks after pre-treatment with pertussis toxin (PTX) into any of 3 different sites in the ventral tegmental area (VTA). An enhanced response to either systemic or intra-accumbens apomorphine occurred only after pre-treatment into the central VTA. Thus, enhanced sensitivity to drugs of either pre- or post-synaptic elements in the nucleus accumbens may develop depending on the site of the PTX pre-treatment within the VTA.

Animals↗

PubMed1997

Amphetamine-induced sensitization and release of dopamine in slices from the ventral tegmental area of rats is enhanced following administration of cholera toxin into the ventral tegmental area.

Administration of cholera toxin (CTX) into the ventral tegmental area (VTA) markedly potentiates the development of behavioral sensitization to amphetamine. Experiments were conducted to determine whether this phenomenon is associated with altered dopamine release from the VTA and nucleus accumbens (NAC). Adult, male rats received bilateral injections of CTX (0-1 microgram) or its vehicle into the VTA. Half of the animals then received four injections of amphetamine (0.5 mg/kg, i.p.) given every other day, while the other half received no additional treatments. In both groups, locomotor responses to amphetamine (0.5 mg/kg, i.p.) were measured on experimental day 18. One day later, amphetamine-induced [3H]dopamine release was measured in tissue slices of the VTA and NAC. Amphetamine-induced locomotor activity was augmented in rats receiving 0.5 or 1.0 microgram intra-VTA CTX pretreatment and the repeated amphetamine regimen. Amphetamine-induced [3H]dopamine release was increased from VTA but not NAC slices obtained from animals showing this behavioral sensitization. Thus, intra-VTA CTX treatment facilitates sensitization to low doses of repeated amphetamine which appears to be associated with the increased ability of this psychostimulant to release dopamine in the VTA.

Amphetamine↗

PubMed1997

Long-term results of treatment of traumatic coxofemoral joint dislocation in dogs: 64 cases (1973-1992).

OBJECTIVE: To determine long-term results of various treatments for traumatic coxofemoral joint dislocation in dogs. DESIGN: Retrospective case series. ANIMALS: 64 dogs that underwent closed reduction and bandage stabilization, extracapsular suture stabilization, transacetabular pinning, toggle pinning, DeVita pinning, or femoral head and neck excision. PROCEDURE: Follow-up evaluations included owner evaluation (64 dogs), physical evaluation (23), and radiography (19). Follow-up time ranged from 8 to 156 months. RESULTS: Owner evaluation scores after closed reduction were significantly better than scores after DeVita pinning, extracapsular suture stabilization, and femoral head and neck excision. On physical examination, 6 of 23 dogs were lame on the side of the previous dislocation. Signs of pain and crepitation were evident during palpation of 12 and 8 of 25 joints, respectively. Thirteen of 21 joints had radiographic evidence of degenerative joint disease. There was a greater progression of degenerative joint disease in previously dislocated joints than in unaffected joints. There were not any significant differences between treatments in regard to results of physical and radiographic evaluation. Time between trauma and treatment and existence of concomitant injuries did not influence follow-up results, but there was a significant association between body weight and radiographic evaluation score. CLINICAL IMPLICATIONS: Concomitant injuries do not appear to justify a worse prognosis in dogs with traumatic coxofemoral joint dislocation, nor does a delay in treatment of > 3 days. Gait abnormalities and degenerative joint disease might develop in the long term. Proper body weight should be maintained regardless of treatment.

Animals↗

PubMed1997

Robust sensitization to amphetamine following intra-VTA cholera toxin administration.

Studies were conducted regarding the hypothesis that enhanced cAMP formation in the ventral tegmental area (VTA) affects the magnitude of the behavioral responses elicited by psychostimulant drugs. In the first paradigm, spontaneous and amphetamine-elicited locomotor activity was measured at various times following injection of cholera toxin (CTX), a known activator of adenylate cyclase, into the VTA. Adult male rats showed enhanced amphetamine-stimulated locomotor activity when tested 1 or 3 days after treatment with 0.5 microgram CTX into the VTA. Spontaneous activity was markedly increased 1 and 3 days following treatment with the higher dose of 1.0 microgram CTX into the VTA, and amphetamine was still capable of eliciting an increased level of locomotor activity above this high baseline. Using a paradigm in which repeated amphetamine injections were given on an intermittent schedule following injection of CTX into the VTA, it was observed that a single low dose of amphetamine (0.5 mg/kg) given 1 day after CTX (0.5 microgram) injection into the VTA led to a markedly potentiated locomotor activity response to subsequent treatment with amphetamine. Evaluation of this protocol (initial amphetamine dose 24 h after CTX injection, and challenge treatment of amphetamine at various times thereafter) showed that the sensitization was long-lasting and could be observed after an initial dose of amphetamine as low as 0.1 mg/kg. A sensitized response was also expressed when the challenge dose was given directly into the nucleus accumbens. These data suggest that injection of CTX into the VTA enhances the induction of locomotor sensitization to amphetamine.

Adenylyl Cyclases↗

PubMed1997

Comparison of sensitization elicited by amphetamine and pertussis toxin: characterization of locomotor behavior and limbic dopamine release.

1. Male, Sprague-Dawley rats were pretreated with one of several regimens of repeated, intermittent amphetamine or with a single-dose of intra-VTA pertussis toxin (PTX). 2. An amphetamine challenge dose (0.5 mg/kg, i.p.) produced increased locomotor activity in both amphetamine and pertussis toxin-pretreated rats. 3. The magnitude of activity in PTX pretreated rats exceeded 5-fold that of the amphetamine-pretreated rats. 4. There were no significant differences in the levels of sensitized behavior elicited by 4 distinct amphetamine pretreatment protocols. 5. Neither of the drug pretreatments caused significant changes in the ability of 10 microM amphetamine to promote dopamine efflux from nucleus accumbens or striatal tissue in vitro. 6. The sensitized behaviour cannot be explained by in vitro alterations in pre-synaptic dopamine release, which may suggest an up-regulation of post-synaptic activity.

Amphetamine↗

PubMed1996

Synthesis of chiral 1-(2'-amino-2'-carboxyethyl)-1,4-dihydro-6,7-quinoxaline-2,3-diones: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor agonists and antagonists.

Recently discovered 6,7-disubstituted quinoxaline-2,3-diones, 1, have been found to antagonize specific binding and functional responses to both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainic acid. Although a variety of studies have analyzed the activity of quinoxaline-2,3-diones with various substitutions at positions 6 and 7, there is little information regarding the effects of N-substitution. A racemic mixture of 1-(2'-amino-2'-carboxyethyl)-1,4-dihydroquinoxaline-2, 3-dione (QXAA, 2, R1 = R2 = H) has been synthesized from 1 (R1 = R2 = H). This compound inhibited specific [3H]AMPA binding but not [3H]kainate binding. IC50 values for QXAA, AMPA, and DNQX were 0.69, 0.012, and 0.74 microM, respectively. The R- and S-enantiomers were prepared by asymmetric synthesis. The S-isomer (2b) was 160-fold more potent in binding assays than the R-isomer (2d), with IC50 values of 0.23 and 38 microM, respectively. Both enantiomers were agonists in a functional assay, with the S-isomer having an EC50 value of 3 microM while that for the R-isomer was greater than 1 mM. Methyl substitutions at positions 6 and 7 (2a and 2c) resulted in antagonist compounds characterized by the S- and R-isomers being nearly equipotent, with IC50 values of 51 and 22 microM in the binding assay and EC50 values of 290 and 300 microM in the functional assay. AMPA had an EC50 value of 11 microM and DNQX an EC50 value of 30 microM in the functional assay. Analogs of quinoxalinediones with side chains other than an amino acid moiety on the nitrogen did not show good binding activities.

Animals↗

PubMed1996

Magnetic resonance imaging and biological changes in injured intervertebral discs under normal and increased mechanical demands.

STUDY DESIGN: An animal model was used to examine the short-term tissue response to changes in the mechanical environment after the structure (disc) is mechanically injured. OBJECTIVES: To observe changes in an injured intervertebral disc and the corresponding motion segment when the mechanical demands of the disc were increased by fusion of the adjacent motion segments. SUMMARY OF BACKGROUND DATA: Disc degeneration has been modeled in animals by producing a tear in the anulus via laminectomy, laparotomy, or posterolaterally. Methods of altering and quantifying the mechanics of the intervertebral joint by use of internal fixation and fusion in the canine have been developed. METHODS: Eight dogs divided into two groups (a study and a control group) had anular stab wounds (L2-L3). The study group was surgically instrumented posteriorly from L3 to L7. Magnetic resonance imaging studies were conducted for all animals before and periodically after the surgical procedures. At the end of the study, the segments were processed histologically and biochemically. RESULTS: Anular bulging was seen on magnetic resonance imaging in all control animals 4 months after injury and did not progress out until 6 months after injury. Similar changes were seen in study animals, but 75% were herniated by 6 months. Histologic changes correlated with magnetic resonance imaging changes. No significant difference in water or proteoglycan content of the disc tissue between groups was found. CONCLUSIONS: Progression from the bulging of the anulus to herniation was not evident in damaged discs not subjected to adjacent fusions. No change in water or proteoglycan content as a function of altered mechanical state was found, suggesting the short-term effect of the altered mechanics is on the mechanical structure and not on the cells or extracellular matrix.

Animals↗

PubMed1996

Induction of locomotor activity by the glutamate antagonist DNQX injected into the ventral tegmental area.

DNQX, an antagonist of AMPA/kainate receptors, was injected into the ventral tegmental area (VTA) to test the hypothesis that AMPA/kainate receptors in this brain region might be involved in regulation of locomotor activity. Bilateral injection of 1 microgram DNQX into the VTA increased locomotor activity. In addition, unilateral injection of DNQX into this site produced contraversive turning, which was potentiated by coadministration of amphetamine (1 mg/kg, i.p.). These results suggest that a glutamatergic afferent to the VTA is tonically active in inhibiting locomotor activity. The locomotor stimulation produced by DNQX was not associated with a change in DOPAC/DA level in the nucleus accumbens or the striatum. However, the locomotor stimulation produced by DNQX was markedly attenuated following blockade of dopaminergic receptors by haloperidol (0.5 mg/kg, s.c.) or following dopamine depletion induced by reserpine plus alpha-methyl-para-tyrosine pretreatment. These results suggest that a basal activation of dopaminergic receptors is required for expression of the locomotor activity elicited by DNQX.

Amphetamine↗

PubMed1995

Kinematics of the canine lumbar intervertebral joint. An in vivo study before and after adjacent instrumentation.

STUDY DESIGN: In vivo, canine lumbar spine intervertebral motion was measured before and after instrumentation of caudal segments. The three-dimensional kinematics of the intervertebral joint were described using helical axes and Fourier series. OBJECTIVE: The in vivo three-dimensional kinematics of the intervertebral joint were measured and described. An animal model where intervertebral motion could be repeatedly changed was developed. SUMMARY OF BACKGROUND DATA: The kinematics of intervertebral joints have been described from results of extensive in vitro testing, some limited in vivo testing, and clinically by evaluation of flexion/extension films. In the canine, in vivo intervertebral motion has been described previously, but the method possessed some measurement artifact. METHODS: In vivo, four canines had motion data collected (L2-L3) while the animals walked on a treadmill. L3 To L7 were instrumented in all of the animals and motion testing was repeated 1 and 12 weeks later. Helical axes of motion were determined for each gait cycle. Fourier series were fit to the motion data, helical axis parameters, and Fourier coefficients were all statistically compared (pre- and postinstrumentation). RESULTS: Vertebral rotations (coronal plane) and excursion of the L2/3 facet increased significantly (P < 0.01) after caudal instrumentation. Helical axes were oriented in a ventral direction and only the angle of rotation about the axis changed significantly (P < 0.05) after instrumentation of caudal segments. The Fourier coefficients (amplitudes) showed a significant (P < 0.05) increase in the coronal plane rotations only, after adjacent instrumentation. CONCLUSION: The in vivo kinematics of the intervertebral joint have been completely defined in this study. Some motion characteristics compare very well to human motion. Since motion at an intervertebral joint now can be repeatedly altered, this animal model shows promise as a useful tool for investigation of tissue response to changes in motion at a joint.

Animals↗

PubMed1995

DNQX in the nucleus accumbens inhibits cocaine-induced conditioned place preference.

Several lines of evidence suggest that activation of both AMPA/kainate receptors and dopaminergic receptors in the nucleus accumbens may be required for psychostimulant drug induced reward. However, it has been reported that dopaminergic antagonists fail to block acquisition of conditioned place preference to cocaine. The goal of these experiments was to determine whether AMPA receptor antagonist injected into the nucleus accumbens could block conditioned place preference elicited by cocaine under conditions where dopaminergic antagonists do not inhibit acquisition of place preference. DNQX (1 microgram/0.5 microliter), injected into the nucleus accumbens just before systemic injections of cocaine (20 mg/kg i.p.) during the training sessions, attenuated the acquisition of place preference. This suggests that AMPA receptors are involved in acquisition of place preference to cocaine. By contrast, fluphenazine (2.5 micrograms/0.5 microliter), injected into the nucleus accumbens during training, did not alter cocaine-induced place preference. Analysis of locomotor activity showed that the ability of flyphenazine to inhibit cocaine-induced hyperactivity progressively decreased with each training session. These observations suggest that the failure of dopaminergic antagonists to block cocaine-induced place preference may be related to adaptations occurring following repeated exposure to these drugs. Both DNQX and fluphenazine blocked the expression of conditioned place preference in rats that had been previously trained with cocaine alone. This result suggests that both AMPA and dopaminergic receptors are involved in the expression of a conditioned place preference to cocaine.

Analysis of Variance↗

PubMed1995

Amphetamine induction of c-fos in the nucleus accumbens is not inhibited by glutamate antagonists.

Systemic administration of relatively high doses of amphetamine or cocaine induces expression of c-fos in the rat striatum and nucleus accumbens. The doses of drugs used in such experiments are substantially higher than those needed to produce reward or sensitization. Therefore, it was determined if low doses of amphetamine capable of eliciting reward and sensitization increase levels of c-Fos protein in the nucleus accumbens. Amphetamine, 1 mg/kg, stimulated locomotor activity and increased the number of nucleus accumbens cells immunohistochemically positive for c-Fos protein to approximately 800 cells per section from a control of approximately 100 cells per section. Since glutamate antagonists modify various responses to amphetamine, it was then determined whether activation of glutamate receptors is involved in the induction of c-Fos protein by low doses of amphetamine. The NMDA receptor antagonist MK-801 by itself stimulated locomotor activity but did not alter baseline levels of c-Fos protein. When given before amphetamine, both locomotor activity and extent of c-fos induction were greater than from amphetamine alone. The AMPA receptor antagonist NBQX by itself had no effect on locomotor activity but increased slightly the number of cells positive for c-Fos protein in the nucleus accumbens. When given before amphetamine, locomotor activity was completely attenuated, and the extent of c-fos induction was greater than from amphetamine alone. We conclude that low doses of amphetamine do increase abundance of c-Fos protein in the nucleus accumbens. This action does not correlate with locomotor activity and is independent of activation of glutamate receptors.

Amphetamines↗

PubMed1995

Chronic bicipital tenosynovitis in dogs: 29 cases (1985-1992).

Medical records of 23 dogs with unilateral and 3 dogs with bilateral chronic bicipital tenosynovitis were reviewed. Mean age of affected dogs was 4.6 years (SD, 2.0 years), and mean body weight was 32.6 kg (SD, 14.5 kg). Neither a breed nor a gender predilection was detected. All dogs had a history of intermittent or progressive weight-bearing lameness that became worse after exercise. Mean duration of lameness prior to medical or surgical treatment was 6.5 months (range, 0.25 to 24 months). In all dogs, signs of pain were evident during palpation of the biceps tendon within the intertubercular groove. Radiography revealed sclerosis or osteophytosis of the intertubercular groove in all 29 shoulder joints. Mild degenerative joint disease was evident radiographically in 17. Arthrography was performed in 12 joints, and in 11 there were irregularities of or filling defects along the biceps tendon. Arthrocentesis was performed on 17 joints; 14 synovial fluid samples had cytologic abnormalities consistent with degenerative joint disease. Medical treatment, consisting of injection of methylprednisolone acetate into the biceps tendon and its synovial sheath, was attempted in 21 of the 29 affected shoulder joints. Surgery, which consisted of tenodesis of the biceps tendon, was attempted in 14 joints; 8 of these had not been treated medically; the remaining 6 had poor results following medical treatment. Gross and histologic findings consistent with chronic bicipital tenosynovitis were observed in all 14 joints in which surgery was performed. Seventeen of the medically treated shoulders were available for clinical evaluation, and results were excellent or good in 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Biomechanical properties of canine corticocancellous bone frozen in normal saline solution.

Eleven pairs of canine metacarpal bones, 10 pairs of metatarsal bones, and 7 pairs of ribs were harvested cleanly and prepared for banking at -20 C for 1 year. One bone of each pair was randomly assigned to 1 type of storage: plastic pack vs immersion in a normal solution of sodium chloride. The contralateral bone was assigned to the opposite treatment. Six pairs of metacarpal bones and 5 pairs of metatarsal bones were tested in torsion to failure. No significant difference was found within pairs. All ribs, 5 pairs of metacarpal bones, and 5 pairs of metatarsal bones were loaded in 4-point bending to failure. The energy absorbed at failure and the ultimate displacement of ribs and metacarpal and metatarsal bones were increased by 25 to 30% and 18 to 24%, respectively, when the bones were frozen in isotonic saline solution. Corticocancellous grafts frozen in normal saline solution are biomechanically less fragile and brittle than grafts stored in plastic without saline solution.

Animals↗

PubMed1994

Comparison of in vivo and in vitro adjacent segment motion after lumbar fusion.

STUDY DESIGN: For in vitro studies, there is no basis for choosing a "load control study" over a "displacement control" study. This study qualitatively compared results from in vitro and in vivo tests, allowing the authors to address the experimental assumptions that in vitro testing contributes to the understanding of the in vivo condition. OBJECTIVES: To compare motion changes at segments adjacent to fusions for in vitro and in vivo tests. SUMMARY OF BACKGROUND DATA: Investigators have measured the effects of spinal fusions on the adjacent segment in a human cadaver model and found greater adjacent facet joint load after fusions. Others have found significant increases in motion and facet loads at segments adjacent to in vitro lumbosacral and long fusions, when the same range of motion was repeated before and after immobilization of lumbar segments. METHODS: L2-L3 motion was measured in vitro by an instrumented spatial linkage under load and displacement control before and after immobilization of segments (L3-L7). In vivo, L2-L3 motion was measured while animals walked on a treadmill. L3-L7 was fused and the L2-L3 motion testing was repeated. The change in in vivo adjacent segment motion was qualitatively compared with the in vitro change under "load" and "displacement" control. RESULTS: Under "load" control, in vitro facet motion did not significantly change after immobilization, whereas under "displacement" control, the facet motion significantly increased from 2.2 +/- 0.4 mm to 4.1 +/- 0.6 mm. Post-instrumentation, in vivo L2-L3 facet motion increased significantly. This change in vivo related better to the changes seen in the in vitro "displacement" control test than to the in vitro "load" control test.

Animals↗

PubMed1994

Interaction of permanently charged metoclopramide analogs with D-2 dopamine receptors.

1. The binding of permanently charged benzamides to the D-2 dopamine receptor of striatal membranes was compared with that of tertiary amine benzamides. 2. The permanently charged benzamides were able to inhibit the binding of [3H]-spiperone to striatal membranes but were less potent than the corresponding tertiary amines. 3. Removal of sodium or decreasing the pH from 7.8 to 6.2 decreased the binding of all benzamides tested, but the permanently charged analogs were affected less by these changes than the tertiary amines. 4. These results suggest that while the binding properties of the permanently charged benzamides are similar to those of the tertiary amine benzamides, there are differences in the manner in which these compounds interact with the D-2 receptor.

Animals↗

PubMed1993

Effects of the AMPA/kainate receptor antagonist DNQX in the nucleus accumbens on drug-induced conditioned place preference.

Activation of AMPA/kainate glutamatergic receptors in the nucleus accumbens may be a component of the mechanism of drug induced reward. To test this hypothesis, 6,7-dinitroquinoxaline-2,3-dione (DNQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)/kainate glutamatergic receptor anatagonist, was injected into the nucleus accumbens before the administration of amphetamine or morphine during the training phase (acquisition) of a conditioned place preference paradigm. Rats were then tested for place preference in the absence of drugs. In other experiments, DNQX was given before testing for place preference (expression) but not during the training phase. Bilateral injection of DNQX (1 microgram/0.5 microliters/side) inhibited acquisition of place preference to amphetamine (1 mg/kg) but not morphine (10 mg/kg). During acquisition, DNQX marginally attenuated the locomotor stimulation elicited by amphetamine during the first but not subsequent training sessions, while the combination of morphine plus DNQX produced marked akinesia during each training session. When given prior to testing, DNQX inhibited the expression of place preference induced by amphetamine and morphine but did not affect locomotor activity. The results suggest that activation of AMPA/kainate receptors is involved in the primary reward stimulation (acquisition of place preference) of amphetamine but not morphine and in behaviors elicited by memory of primary reward stimulation (expression of place preference) for both drugs. Furthermore, locomotor activity during conditioning is not necessary for acquisition of place preference.

Amphetamine↗