PubMed Health⌕ Search

Biomedical subjects

J S Rhodes

Publications and source records attributed to J S Rhodes.

At least 19 recordsLinked to original sources

Mouse inbred strain differences in ethanol drinking to intoxication.

Recently, we described a simple procedure, Drinking in the Dark (DID), in which C57BL/6J mice self-administer ethanol to a blood ethanol concentration (BEC) above 1 mg/ml. The test consists of replacing the water with 20% ethanol in the home cage for 4 h early during the dark phase of the light/dark cycle. Three experiments were conducted to explore this high ethanol drinking model further. In experiment 1, a microanalysis of C57BL/6J behavior showed that the pattern of ethanol drinking was different from routine water intake. In experiment 2, drinking impaired performance of C57BL/6J on the accelerating rotarod and balance beam. In experiment 3, 12 inbred strains were screened to estimate genetic influences on DID and correlations with other traits. Large, reliable differences in intake and BEC were detected among the strains, with C57BL/6J showing the highest values. Strain means were positively correlated with intake and BEC in the standard (24 h) and a limited (4 h) two-bottle ethanol vs. water test, but BECs reached higher levels for DID. Strain mean correlations with other traits in the Mouse Phenome Project database supported previously reported genetic relationships of high ethanol drinking with low chronic ethanol withdrawal severity and low ethanol-conditioned taste aversion. We extend these findings by showing that the correlation estimates remain relatively unchanged even after correcting for phylogenetic relatedness among the strains, thus relaxing the assumption that the strain means are statistically independent. We discuss applications of the model for finding genes that predispose pharmacologically significant drinking in mice.

Alcohol Drinking↗

The evolution of gene expression in mouse hippocampus in response to selective breeding for increased locomotor activity.

The evolution of behavior has been notoriously difficult to study at the molecular level, but mouse genetic technology offers new promise. We applied selective breeding to increase voluntary wheel running in four replicate lines of Mus domesticus (S mice) while maintaining four additional lines through random breeding to serve as controls (C mice). The goal of the study was to identify the gene expression profile of the hippocampus that may have evolved to facilitate the increased voluntary running. The hippocampus was of interest because it is known to display marked physiological responses in association with wheel running itself. We used high-density oligonucleotide arrays representing 11,904 genes. To control for the confounding influence of physical activity itself on gene expression, animals were housed individually without access to running wheels, and were sampled during the day when they are normally inactive. Two-month-old female mice in estrus were used (n = 16 total; two per line; 8 S and 8 C). After correcting for an acceptable false discovery rate (10%), 30 genes, primarily involved in transcription and translation, significantly increased expression whereas 23 genes, distributed among many categories including immune function and neuronal signaling, decreased expression in S versus C mice. These changes were relatively small in magnitude relative to the changes in gene expression that occur in the hippocampus in response to wheel running itself. A priori tests of dopamine receptor expression levels demonstrated an increase of approximately 20% in the expression of D2 and D4 receptors. These results suggest that relatively small changes in the expression patterns of hippocampal genes underlie large changes in phenotypic response to selection, and that the genetic architecture of running motivation likely involves the dopaminergic system as well as CNS signaling machinery.

Analysis of Variance↗

Brimonidine purite 0.15% versus dorzolamide 2% each given twice daily to reduce intraocular pressure in subjects with open angle glaucoma or ocular hypertension.

BACKGROUND/AIMS: To evaluate the efficacy of brimonidine purite versus dorzolamide given twice daily in primary open angle glaucoma or ocular hypertensive subjects. METHODS: In this double masked, multicentre, prospective, crossover comparison 33 subjects were randomised to brimonidine purite or dorzolamide for the first 4 week treatment period after a 4 week washout. Subjects began the opposite treatment for the second 4 week period after another 4 week washout. Intraocular pressure (IOP) was measured at 08:00 (trough) and 10:00, 18:00, and 20:00 hours after dosing at each baseline and at the end of each treatment period. RESULTS: The baseline diurnal IOP was 22.9 (SD 2.8) for brimonidine purite and 22.2 (SD 2.4) mm Hg for dorzolamide. The trough IOP following 4 weeks of therapy was 21.0 (SD 3.7) for brimonidine purite and 21.0 (SD 3.1) mm Hg for dorzolamide (p = 0.90). The mean diurnal IOP was 19.3 (SD 3.1) for brimonidine purite and 19.8 (SD 2.4) mm Hg for dorzolamide (p = 0.46). Dorzolamide caused more ocular stinging upon instillation (n = 8) than brimonidine purite (n = 1) (p = 0.02). No statistical differences existed between groups for systemic adverse events. CONCLUSIONS: This study suggests that brimonidine purite and dorzolamide each given twice daily have similar efficacy in primary open angle glaucoma or ocular hypertensive subjects. However, a trend was observed at 10:00 of greater brimonidine purite efficacy compared with dorzolamide.

Antihypertensive Agents↗

Root canal retreatment: 2. Practical solutions.

Root canal retreatment is often the preferred method of treating a tooth in which root canal treatment has failed. Part two of this two-part article discusses the rationale for root canal retreatment and practical techniques and equipment that are available to practitioners.

Dental Pulp Cavity↗

Assessment of potential carbon dioxide reductions due to biomass-coal cofiring in the United States.

Cofiring biomass with coal in existing power plants offers a relatively inexpensive and efficient option for increasing near-term biomass energy utilization. Potential benefits include reduced emissions of carbon dioxide, sulfur, and nitrogen oxides and development of biomass energy markets. To understand the economics of this strategy, we develop a model to calculate electricity and pollutant mitigation costs with explicit characterization of uncertainty in fuel and technology costs and variability in fuel properties. The model is first used to evaluate the plant-level economics of cofiring as a function of biomass cost. It is then integrated with state-specific coal consumption and biomass supply estimates to develop national supply curves for cofire electricity and carbon mitigation. A delivered cost of biomass below 15 dollars per ton is required for cofire to be competitive with existing coal-based generation. Except at low biomass prices (less than 15 dollars per ton), cofiring is unlikely to be competitive for NOx or SOx control, but it can provide comparatively inexpensive control of CO2 emissions: we estimate that emissions reductions of 100 Mt-CO2/year (a 5% reduction in electric-sector emissions) can be achieved at 25 +/- 20 dollars/tC. The 2-3 year time horizon for deployment--compared with 10-20 years for other CO2 mitigation options--makes cofiring particularly attractive.

Air Pollutants↗

Differential sensitivity to acute administration of Ritalin, apomorphine, SCH 23390, but not raclopride in mice selectively bred for hyperactive wheel-running behavior.

RATIONALE: Previous studies of mice ( Mus domesticus) selectively bred for high voluntary wheel running have suggested that the hyperactivity is associated with dysfunction in the dopaminergic neuromodulatory system and that high-running mice may represent a useful genetic model for attention deficit hyperactivity disorder (ADHD). OBJECTIVES: We tested the hypothesis that mice from the four replicate hyperactive lines would respond differently to methylphenidate (Ritalin), apomorphine (non-selective dopamine agonist), SCH 23390 (selective D1-like dopamine antagonist), and raclopride (selective D2-like dopamine antagonist) than individuals from the four replicate, randomly bred, control lines. METHODS: After animals were habituated (3 weeks) to their cages with attached wheels, drugs were administered via intraperitoneal injections, at night, during peak wheel-running activity. Revolutions on wheels 10-70 min post-injection were used to quantify drug responses. RESULTS: Ritalin (15 mg/kg and 30 mg/kg) increased wheel running in control lines but decreased running in selected lines. A low-dose (0.125 mg/kg) of apomorphine reduced wheel running by a similar amount in control and selected lines; however, higher doses of apomorphine (0.25 mg/kg and 0.5 mg/kg) produced greater reductions in wheel running in the control lines. SCH 23390 (0.025, 0.05, and 0.1 mg/kg) caused greater reductions in wheel running in control than in selected lines. Raclopride (0.5, 1, and 2 mg/kg) reduced wheel running by a similar amount in control and selected lines. CONCLUSIONS: These results support the interpretation that genetically determined hyperactive wheel-running behavior is associated with altered dopaminergic function in this mouse model. More specifically, results suggest that D1-like (D1 or D5), but not D2-like (D2, D3, or D4), dopamine receptors have reduced function in the high-running mice. The fact that Ritalin decreased wheel running in selected lines further supports their use as an animal model of ADHD.

Animals↗

Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running.

Voluntary wheel running in rats increases hippocampal brain-derived neurotrophic factor (BDNF) expression, a neurochemical important for neuronal survival, differentiation, connectivity and synaptic plasticity. Here, we report the effects of wheel running on BDNF and neurotrophin-3 (NT-3) protein levels in normal control mice, and in mice selectively bred (25 generations) for increased voluntary wheel running. We hypothesized that increased voluntary wheel running in selected (S) mice would increase CNS BDNF and NT-3 protein levels more than in control (C) mice. Baseline hippocampal BDNF levels (mice housed without running wheels) were similar in S and C mice. Following seven nights of running, hippocampal BDNF increased significantly more in S versus C mice, and levels were correlated with distance run (considering C and S mice together). Spinal and cerebellar BDNF and hippocampal NT-3 levels were not significantly affected by wheel running in any group, but there was a small, positive correlation between spinal C3-C6 BDNF levels and distance run (considering C and S mice together). This is the first study to demonstrate that mice which choose to run more have greater elevations in hippocampal BDNF, suggesting enhanced potential for exercise-induced hippocampal neuroplasticity.

Animals↗

Strain differences in three measures of ethanol intoxication in mice: the screen, dowel and grip strength tests.

Mice from 8 to 21 inbred strains were tested for sensitivity to ethanol intoxication using a range of doses and three different measures: the screen test, the dowel test and a test of grip strength. Strains differed under nearly all conditions. For the dowel test, two dowel widths were employed, and mice were tested immediately or 30 min after ethanol. For the dowel and screen tests, low doses failed to affect some strains, and the highest doses failed to discriminate among mice, maximally affecting nearly all. For grip strength, a single ethanol dose was used, and mice of all strains were affected. Pharmacokinetic differences among strains were significant, but these could not account for strain differences in intoxication. For doses and test conditions in the middle range, there were only modest correlations among strain means within a test. In addition, genotypic correlations across tests were modest to quite low. These results suggest that different specific versions of a test reflect the influence of different genes, and that genetic influences on different tests were also distinct.

Alcoholic Intoxication↗

Differential sensitivity to acute administration of cocaine, GBR 12909, and fluoxetine in mice selectively bred for hyperactive wheel-running behavior.

RATIONALE: To study the neural basis of genetic hyperactivity, we measured acute drug responses of mice (Mus domesticus) from four replicate lines that had been selectively bred (23-24 generations) for increased running-wheel activity. OBJECTIVES: We tested the hypothesis that the high-running lines would respond differently to cocaine, GBR 12909, and fluoxetine (Prozac) compared with four replicate, random-bred, control lines. We also tested the hypothesis that the high-running lines would display hyperactivity in cages without wheels. METHODS: Drug trials were conducted at night, during peak activity, after animals were habituated (3 weeks) to their cages with attached wheels. Revolutions on wheels 10-40 min post-injection were used to quantify drug responses. In a separate study, total photobeam breaks (produced on the first and second 24-h period of exposure) were used to quantify basal activity in animals deprived of wheels. RESULTS: Cocaine and GBR 12909 decreased wheel running in selected lines by reducing the average speed but not the duration of running, but these drugs had little effect in control lines. Fluoxetine reduced running speed and duration in both selected and control animals, and the magnitude of the reduction was proportional to baseline activity. Basal activity in animals deprived of wheels (quantified using photobeam breaks) was significantly higher in selected than control lines on the second day of testing. CONCLUSIONS: These results suggest an association between genetically determined hyperactive wheel-running behavior and dysfunction in the dopaminergic neuromodulatory system. Our selected lines may prove to be a useful genetic model for attention deficit hyperactivity disorder.

Animals↗

Open-field behavior of house mice selectively bred for high voluntary wheel-running.

Open-field behavioral assays are commonly used to test both locomotor activity and emotionality in rodents. We performed open-field tests on house mice (Mus domesticus) from four replicate lines genetically selected for high voluntary wheel-running for 22 generations and from four replicate random-bred control lines. Individual mice were recorded by video camera for 3 min in a 1-m2 open-field arena on 2 consecutive days. Mice from selected lines showed no statistical differences from control mice with respect to distance traveled, defecation, time spent in the interior, or average distance from the center of the arena during the trial. Thus, we found little evidence that open-field behavior, as traditionally defined, is genetically correlated with wheel-running behavior. This result is a useful converse test of classical studies that report no increased wheel-running in mice selected for increased open-field activity. However, mice from selected lines turned less in their travel paths than did control-line mice, and females from selected lines had slower travel times (longer latencies) to reach the wall. We discuss these results in the context of the historical open-field test and newly defined measures of open-field activity.

Animals↗

The efficacy of gutta-percha removal using ProFiles.

AIM: The purpose of this study was to compare the efficacy in vitro of gutta-percha removal from obturated root canals using ProFiles. METHODOLOGY: Forty-eight human root canals with curvatures ranging between 25 and 45 degrees were instrumented by a standardized method to an apical ISO size 30 and 0.04 taper. They were obturated with vertically condensed gutta-percha. Retreatment was performed with the following techniques: K-Flexofiles with chloroform; Hedstrom files with chloroform; ProFiles 0.04 taper with chloroform; ProFiles 0.04 taper alone. The time for each method was measured. A microfocal macroradiographic technique was used to evaluate the amount of debris remaining within the root canals after the retreatment procedure. Roots were divided into apical, middle and coronal parts and scored on a scale of 0 (no debris) to 3 (> 50% of walls covered with debris) by trained observers on two separate occasions. RESULTS: The scores for debris remaining within root canals for K-Flexofiles with chloroform and ProFiles with chloroform were the lowest and not significantly different at all three levels of the roots examined (P > 0.05), and Hedstrom files with chloroform and ProFiles with chloroform were not significantly different in the apical part. In general, coronal parts were cleaner than apical parts. The difference in scores at the three levels between ProFiles with chloroform and ProFiles alone were each significant (P < 0.01). Instrumentation using ProFiles with chloroform (mean 6.42 min) was significantly faster than using hand files (mean 11.67 min) (P < 0.01). CONCLUSION: The results indicated that ProFiles or hand files with chloroform produced similarly clean canals, but that ProFiles were faster.

Chloroform↗

A case of unusual anatomy: a mandibular second premolar with four canals.

AIM: The aim of this case report is to describe conventional root canal treatment on a mandibular second premolar with four canals. SUMMARY: The pulp of a mandibular second premolar had become irreversibly inflamed, probably as a result of bacterial microleakage from a carious lesion. The general dental practitioner had initiated root canal treatment, but due to procedural difficulties referred the case. Conventional root canal treatment was then performed with magnification. Preparation was undertaken in a crown-down manner using balanced force hand instrumentation with flexible K-type files and files of Greater Taper. The root canals were obturated with vertically condensed gutta-percha technique. KEY LEARNING POINTS: Good illumination and magnification are vital during root canal treatment. Crown-down preparation using the balanced force technique with flexible files makes instrumentation easier and prevents many of the procedural errors that can occur with filing techniques. Greater Taper instruments made of nickel-titanium are sufficiently flexible to be used in complex curved canals and obviate the need for step-back flaring of the apical preparation. Vertical compaction of warm gutta-percha may simplify the obturation of complex root canal systems. When the technical difficulty of a procedure exceeds the expertise of the practitioner, specialist referral may be required.

Adult↗

Genetic selection of mice for high voluntary wheel running: effect on skeletal muscle glucose uptake.

Effects of genetic selection for high wheel-running activity (17th generation) and access to running wheels on skeletal muscle glucose uptake were studied in mice with the following treatments for 8 wk: 1) access to unlocked wheels; 2) same as 1, but wheels locked 48 h before glucose uptake measurement; or 3) wheels always locked. Selected mice ran more than random-bred (nonselected) mice (8-wk mean +/- SE = 8,243 +/- 711 vs. 3,719 +/- 233 revolutions/day). Body weight was 5-13% lower for selected vs. nonselected groups. Fat pad/body weight was ~40% lower for selected vs. nonselected and unlocked vs. locked groups. Insulin-stimulated glucose uptake and fat pad/body weight were inversely correlated for isolated soleus (r = -0.333; P < 0.005) but not extensor digitorum longus (EDL) or epitrochlearis muscles. Insulin-stimulated glucose uptake was higher in EDL (P < 0.02) for selected vs. nonselected mice. Glucose uptake did not differ by wheel group, and amount of running did not correlate with glucose uptake for any muscle. Wheel running by mice did not enhance subsequent glucose uptake by isolated muscles.

Animals↗

Selection for high voluntary wheel-running increases speed and intermittency in house mice (Mus domesticus).

In nature, many animals use intermittent rather than continuous locomotion. In laboratory studies, intermittent exercise regimens have been shown to increase endurance compared with continuous exercise. We hypothesized that increased intermittency has evolved in lines of house mice (Mus domesticus) that have been selectively bred for high voluntary wheel-running (wheel diameter 1.12 m) activity. After 23 generations, female mice from four replicate selection lines ran 2.7 times more revolutions per day than individuals from four random-bred control lines. To measure instantaneous running speeds and to quantify intermittency, we videotaped mice (N=41) during a 5-min period of peak activity on night 6 of a 6-day exposure to wheels. Compared with controls (20 revs min(-1) while actually running), selection-line females (41 revs min(-1)) ran significantly faster. These instantaneous speeds closely matched the computer-recorded speeds over the same 5-min period. Selection-line females also ran more intermittently, with shorter (10.0 s bout(-1)) and more frequent (7.8 bouts min(-1)) bouts than controls (16.8 s bout(-1), 3.4 bouts min(-1)). Inter-bout pauses were also significantly shorter in selection-line (2.7 s) than in control-line (7.4 s) females. We hypothesize that intermittency of locomotion is a key feature allowing the increased wheel-running performance at high running speeds in selection-line mice.

Aging↗

A comparison of two nickel-titanium instrumentation techniques in teeth using microcomputed tomography.

AIM: The aim of the study was to compare the shaping of root canals by two nickel-titanium instrumentation techniques using microcomputed tomography (MCT). METHODOLOGY: Ten mandibular first molar teeth (30 canals) that had intact crowns and fully formed roots were scanned using MCT. Fifteen canals were instrumented using NiTiFlex hand files (Maillefer) using balanced force. The remainder were instrumented using prototype ProFile 0.04 Taper instruments (Dentsply) in a crown-down manner to an apical size ISO 25. The teeth were scanned again following instrumentation. The two instrumentation techniques were compared in a total of 27 canals. The area of dentine removed at predetermined levels (2.0, 3.0, 4.5, 6.0, 7.5 mm) from the apex was measured. Transportation and centring were recorded. Images constructed at these levels were compared with video images of equivalent physical sections created after the second scan. The volume of dentine removed in the apical 7.5 mm of the root canals of each tooth was calculated and the different techniques compared. Rendered three-dimensional images were used to assess the preparations qualitatively. The time taken for preparation was recorded. RESULTS: There was no significant difference between hand instrumentation with NitiFlex files and machine instrumentation with prototype ProFile 0.04 Taper instruments for any of the variables tested. CONCLUSIONS: Both techniques produced well centred and tapered preparations.

Dental High-Speed Technique↗

Micro-computed tomography: a new tool for experimental endodontology.

AIM: Micro-computed tomography (MCT) using conebeam geometry is a method of producing true 3D images of the structure of small samples. A prototype MCT unit was adapted for imaging teeth to examine whether it could be used to quantify the instrumentation of root canals. METHODOLOGY: Ten mandibular first molar teeth that had intact crowns and fully formed roots were scanned using MCT at a resolution of 0.081 mm and 3D-rendered images created; root canals were segmented from this. Reproducibility of MCT was verified for root canal shape and size. Access cavities were prepared into the pulp space and root canals enlarged to a continously tapering preparation using a crowndown technique. Each tooth was scanned again to allow comparison of pre- and post-instrumentation images. The roots were then sectioned at five predetermined horizontal levels for video-digitized measurement of dimensions of roots and root canals. The video images had a resolution of 0.025 mm. Video-digitized images of the physical cut surfaces were compared with equivalent MCT reconstructed images. The total area of the root canals (internal) and root (external) at each level were calculated from both MCT reconstructions and video-digitized images, and compared. RESULTS: There was a highly significant correlation between MCT and video images for both external and internal areas (r = 0.94). Rendered 3D images were constructed to show the root canal systems of teeth. The total volumes of the apical 7.5 mm of root canals were calculated from rendered images of nine teeth before and after instrumentation. The mean amount of dentine removed by instrumentation was 3.725 mm3, which was 28% of the original canal volume. CONCLUSIONS: Micro-computed tomography was shown to be accurate for experimental endodontology.

Anatomy, Cross-Sectional↗