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Biomedical subjects

Jeffrey E Edwards

Publications and source records attributed to Jeffrey E Edwards.

12 recordsLinked to original sources
PubMed2005

Pre-synaptic modulation of quadriceps arthrogenic muscle inhibition.

Arthrogenic muscle inhibition (AMI) impedes rehabilitation following knee joint injury by preventing activation of the quadriceps. AMI has been attributed to neuronal reflex activity in which altered afferent input originating from the injured joint results in a diminished efferent motor drive to the quadriceps muscles. Beginning to understand the mechanisms responsible for muscle inhibition following joint injury is vital to control or eliminate this phenomenon. Therefore, the purpose of this investigation is to determine if quadriceps AMI is mediated by a presynaptic regulatory mechanism. Eight adults participated in two sessions: in one session their knee was injected with saline and in the other session it was not. The maximum Hoffmann reflex (H-reflex), M-wave, reflex activation history, plasma epinephrine, and norepinephrine were recorded at: baseline, post needle stick, post lidocaine, and 25 and 45 min post effusion. Measures for the control condition were matched to the effusion condition. The percent of the unconditioned reflex amplitude for reflex activation history and the maximum H-reflex were decreased at 25 and 45 min post effusion as compared to measures taken at baseline, post needle stick, and post lidocaine (P<0.05). No differences were noted for the maximum M-wave or plasma epinephrine and norepinephrine levels in either the effusion or noneffusion admission (P>0.05). No differences were detected at any time interval for any measure during the control admission (P>0.05). Quadriceps AMI elicited via an experimental knee joint effusion is, at least in part, mediated by a presynaptic mechanism.

Adult↗
PubMed2005

The metabolism of nonane, a JP-8 jet fuel component, by human liver microsomes, P450 isoforms and alcohol dehydrogenase and inhibition of human P450 isoforms by JP-8.

Nonane, a component of jet-propulsion fuel 8 (JP-8), is metabolized to 2-nonanol and 2-nonanone by pooled human liver microsomes (pHLM). Cytochrome P450 (CYP) isoforms 1A2, 2B6 and 2E1 metabolize nonane to 2-nonanol, whereas alcohol dehydrogenase, CYPs 2B6 and 2E1 metabolize 2-nonanol to 2-nonanone. Nonane and 2-nonanol showed no significant effect on the metabolism of testosterone, estradiol or N,N-diethyl-m-toluamide (DEET), but did inhibit carbaryl metabolism. JP-8 showed modest inhibition of testosterone, estradiol and carbaryl metabolism, but had a more significant effect on the metabolism of DEET. JP-8 was shown to inhibit CYPs 1A2 and 2B6 mediated metabolism of DEET, suggesting that at least some of the components of JP-8 might be metabolized by CYPs 1A2and/or 2B6.

Alcohol Dehydrogenase↗
PubMed2005

Role of P-glycoprotein in distribution of nelfinavir across the blood-mammary tissue barrier and blood-brain barrier.

As a first approach in understanding the possible efficacy and toxicity of human immunodeficiency virus protease inhibitors during breast feeding, the milk-to-plasma ratio of nelfinavir was determined in lactating rats. The milk-to-plasma ratio of nelfinavir was determined to be 0.56 +/- 0.10 (means +/- standard deviations). Western blotting indicated that P-glycoprotein is expressed in rat mammary and brain tissue; however, the multidrug-resistant modulator GF120918 showed a significant effect only at the blood-brain barrier and not at the mammary-epithelial tissue barrier.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

An experimental knee joint effusion does not affect plasma catecholamine concentration in humans.

Knee joint effusion causes quadriceps inhibition and is accompanied by increased soleus muscle excitability. In order to reverse the neurological alterations that occur to the musculature following effusion, we need to understand the extent of neural involvement. Ten healthy adults were tested on two occasions; during one session, subjects had their knees injected with saline and in the other admission, they did not. Soleus Hmax, Mmax, plasma epinephrine, and norepinephrine concentrations were obtained at five intervals. Results showed that Hmax increased following the effusion, while norepinephrine and epinephrine levels were not altered. We suggest that the soleus facilitation seen following knee effusion results from stimulation of joint mechanoreceptors and removal of descending spinal and supraspinal inhibition and is not the result of a sympathetic response.

Adult↗
PubMed2003

Arthrogenic muscle inhibition is not present in the limb contralateral to a simulated knee joint effusion.

OBJECTIVE: The purpose of this investigation was to estimate bilateral neuromuscular activity in the vastus medialis on induction of a unilateral knee joint effusion. DESIGN: Eight subjects each were assigned to effusion or control groups. The effusion group had 60 ml of sterile saline injected into their superolateral knee joint capsules. The control group rested for 8 mins. Bilateral recruitment curves for the Hoffmann reflex (H-reflex) and muscle response (M-wave) were obtained before and 10, 20, and 30 mins after the effusion or rest. The maximum H-reflex (Hmax), maximum M-wave (Mmax), and the Hmax/Mmax ratio were utilized for data analysis. RESULTS: Both Hmax and Hmax/Mmax ratios decreased from the baseline measure in the effused vastus medialis, whereas no changes were detected on the contralateral side. Effused subjects demonstrated decreased motoneuron pool excitability in the effused limb, whereas control subjects did not differ from baseline. CONCLUSIONS: Knee joint effusion results in ipsilateral but not contralateral impairment of quadriceps function. Rehabilitation protocols after knee joint injury should focus on ipsilateral neuromuscular and mechanical alterations that occur as the result of joint damage.

Adult↗
PubMed2003

A single dose of Ginkgo biloba does not affect soleus motoneuron pool excitability.

EGb 761 has been shown to increase acetylcholine synthesis and release and increase cholinergic receptors leading to an increase in cholinergic neurotransmission. These effects may be observed in the neuromuscular system, manifested by changes in motoneuron pool excitability as measured by the Hoffmann reflex to motor response (H/M) ratio. The objective was to determine whether a single dose of EGb 761 affects motoneuron pool excitability of the soleus muscle as measured by the H/M ratio. Following initial soleus H/M measurements, 20 healthy volunteers were randomly assigned to 1 of 3 treatment groups (control, 180 g cellulose placebo, and 180 g EGb 761). H/M ratios were recorded 1, 2, and 3 hours post treatment. A 3 x 4 repeated-measures analysis of variance was used to analyze differences in H/M ratio between treatments. No differences were observed between treatments (p = 0.75) or over time (p = 0.17), and there was not a treatment by time interaction (p = 0.27). A single dose of 180 g of EGb 761 does not affect soleus motoneuron pool excitability.

Adult↗
PubMed2003

Hydromorphone transfer into breast milk after intranasal administration.

STUDY OBJECTIVES: To determine the distribution of hydromorphone into breast milk and the potential exposure of the suckling infant, and whether the distribution of hydromorphone into milk can be predicted accurately by a passive diffusion model. DESIGN: Single-dose, pharmacokinetic study. SETTING: University clinical research unit. PATIENTS: Eight lactating, nonsmoking, healthy women aged 24-32 years. INTERVENTION: Hydromorphone HCl 2 mg was given intranasally to the women to characterize its pharmacokinetics and extent of its transfer into breast milk. MEASUREMENTS AND MAIN RESULTS: Plasma and milk samples were analyzed using liquid chromatography with tandem mass spectrometry detection. The milk:plasma ratio (M:P) was calculated as the total area under the concentration-time curve (AUC) of the milk divided by the total AUC of the plasma. Predicted in vitro M:P ratios were calculated using a diffusion model. Protein binding in milk and plasma, partitioning into milk fat (whole milk:skim milk ratios), as well as pH partitioning between plasma and milk were incorporated in the model. Protein binding was determined by equilibrium dialysis. Protein binding was minimal in both milk and plasma, with unbound fractions of 1 and 0.84, respectively There was little partitioning into milk fat, as demonstrated by the whole milk:skim milk ratio of 0.98. The observed and predicted M:P ratios +/- SD for hydromorphone were 2.57 +/- 0.47 and 1.11 +/- 0.28, respectively. The 95% confidence interval for the observed M:P ratio overlapped the confidence interval of the predicted M:P ratio, a finding that supports a role for both passive diffusion and active transport as mechanisms of hydromorphone transfer into milk. CONCLUSION: Hydromorphone distributes rapidly from plasma into breast milk; however, the drug does not partition into fat. The suckling infant would receive approximately 0.67% of the maternal dose of hydromorphone (adjusted for body weight). As this is a limited exposure, further studies are needed to determine any potential impact to an infant who is fed breast milk from a mother treated with hydromorphone.

Administration, Intranasal↗
PubMed2002

Preliminary comparison of bromelain and Ibuprofen for delayed onset muscle soreness management.

OBJECTIVE: The purpose of this study was to determine whether a common bromelain regimen or common ibuprofen regimen are effective in resolving pain and muscle dysfunction associated with delayed onset muscle soreness of the elbow flexors. DESIGN: A randomized, double-blinded, repeated measures design was used for this study. SETTING: The study was performed in the Sports Injury Research Lab at an NCAA Division I university. PARTICIPANTS: Forty subjects who had not participated in an upper body resistance-training program 3 months prior to the study, suffered pain or injury in the nondominant arm, or experienced an adverse response to nonsteroidal anti-inflammatory drugs or pineapple (bromelain source) were recruited. Thirty-nine subjects finished the study. INTERVENTIONS: Active range of motion (ROM), perceived pain, and peak concentric torque measurements of the nondominant arm were taken prior to and 24, 48, 72, and 96 hours following an eccentric exercise protocol of the elbow flexors. Subjects were assigned to one of four treatment groups (bromelain 300 mg t.i.d., ibuprofen 400 mg t.i.d., placebo t.i.d., and control) and began treatment immediately following the exercise protocol. MAIN OUTCOME MEASURES: No differences among treatments were observed for any of the dependent variables at any time. ROM deficits and pain peaked between 48 and 72 hours. Peak torque deficiencies were observed between 24 and 72 hours. CONCLUSIONS: Ingestion of bromelain and ibuprofen had no effect on elbow flexor pain, loss of ROM, or loss of concentric peak torque as a result of an eccentric exercise regimen.

Adolescent↗
PubMed2002

Effects of a P-glycoprotein inhibitor on brain and plasma concentrations of anti-human immunodeficiency virus drugs administered in combination in rats.

Most of the existing anti-human immunodeficiency virus agents enter the central nervous system (CNS) inefficiently and thus may allow slow viral replication in the brain. This may provide a sanctuary for the virus in the CNS and contribute to the development of acquired immunodeficiency syndrome dementia complex. This study evaluates a prodrug approach to improve the CNS delivery of the reverse transcriptase inhibitor 2',3'-dideoxyinosine (ddI) in combination with inhibition of P-glycoprotein-mediated efflux to increase the CNS delivery of the protease inhibitor nelfinavir and to determine whether any unanticipated drug interactions occur in this combination therapy. Three rats received either 6-chloro-2'3'-dideoxypurine (6-Cl-ddP), a prodrug of ddI activated by adenosine deaminase, nelfinavir, nelfinavir and 6-Cl-ddP, nelfinavir and N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918) (a P-glycoprotein inhibitor), 6-Cl-ddP and GF120918, or 6-Cl-ddP, nelfinavir, and GF120918. Both 6-Cl-ddP and nelfinavir were administered as i.v. infusions, whereas GF120918 was given as an i.v. bolus 2 h before sampling. Plasma and brain tissue concentrations of 6-Cl-ddP, ddI, and nelfinavir were determined. Neither nelfinavir nor GF120918 was shown to alter the brain/plasma ratios of 6-Cl-ddP or ddI. GF120918, however, increased the plasma concentrations of 6-Cl-ddP and ddI, resulting in increased brain concentrations. GF120918 increased the brain/plasma ratio of nelfinavir significantly (approximately 100-fold). The brain/plasma ratios of nelfinavir were reduced nearly 2-fold in rats treated with nelfinavir, 6-Cl-ddP, and GF120918 compared with rats receiving only nelfinavir and GF120918, suggesting a modest inhibition of nelfinavir uptake by 6-Cl-ddP. Overall, combined 6-Cl-ddP, nelfinavir, and GF120918 administration enhances the brain/plasma ratios of both ddI and nelfinavir.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

GF120918, a P-glycoprotein modulator, increases the concentration of unbound amprenavir in the central nervous system in rats.

The goal of this study was to determine the distribution of unbound amprenavir in the central nervous system (CNS) of rats. The concentration of unbound amprenavir in the extracellular fluid of the brain and the blood was examined in the presence and absence of the MDR modulator GF120918 by microdialysis. The brain-to-blood ratio of amprenavir in the absence and presence of GF120918 was found to be significantly different (P < 0.003; 0.076 and 0.617, respectively). The use of the MDR modulator GF120918 could potentially increase the penetration of human immunodeficiency virus protease inhibitors into the CNS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Peripheral ankle cooling and core body temperature.

CONTEXT: Exposure of the human body to cold is perceived as a stressor and results in a sympathetic response geared at maintaining core temperature. Application of ice to the periphery may lead to a decrease in core temperature, which may counteract the therapeutic effects of cryotherapy. OBJECTIVE: To determine if core temperature is lowered by the application of an ice bag to the ankle joint complex. DESIGN: A within-subjects, repeated-measures design. SETTING: The University of Virginia General Clinical Research Center. PATIENTS OR OTHER PARTICIPANTS: Twenty-three healthy adults aged 19 to 39 years. INTERVENTION(S): Subjects were admitted to the hospital on 2 separate occasions. During one admission, subjects had a 20-minute ice treatment applied to their ankles; in the other admission, a bag of marbles was applied. Temperature measurements were recorded at 6 time intervals: baseline (before ice application), immediately after ice application, 10 and 20 minutes after ice application, and 10 and 20 minutes after ice removal. MAIN OUTCOME MEASURE(S): We measured core temperature and ankle and soleus muscle surface temperatures. A mixed-effects model analysis of variance with repeated measures was used to determine if differences existed in core temperature and ankle and soleus surface temperatures between conditions (cryotherapy and control) and over time. RESULTS: Core temperature did not change after ice application or ice removal (P > 0.05). The average core temperatures during the cryotherapy and control conditions were 36.72 degrees C +/- 0.42 degrees C and 36.45 degrees C +/- 1.23 degrees C, respectively. CONCLUSIONS: A 20-minute cryotherapy treatment applied to the ankle did not alter core temperature.

Journal Article↗