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Biomedical subjects

J D Davis

Publications and source records attributed to J D Davis.

At least 55 records · Page 3Linked to original sources

Deterministic and probabilistic control of the behavior of rats ingesting liquid diets.

The probability distributions of bouts of licking and pauses between them in rats ingesting sucrose solutions were studied to determine if the durations of these ingestive and noningestive acts were controlled by a deterministic or probabilistic decision rule in the central nervous system. The duration of the bouts of licking could be modeled by a Poisson process, indicating that these bouts were terminated by a probabilistic rule. Three different types of pauses terminated the bouts of licking. Each averaged 0.3, 1.5, or 50-60 s in duration. The two longer pauses could be modeled by a Poisson process, indicating that their termination was also probabilistic in nature. The shorter pauses averaging 0.3 s could not and are more likely deterministically controlled.

Animals↗

Interaction between orosensory and postingestional stimulation in the control of corn oil intake by rats.

The microstructure of the ingestive behavior of rats ingesting corn oil emulsions was analyzed to describe quantitatively how postingestional stimulation interacts with orosensory stimulation to control the intake of corn oil. Seventeen hour food deprived rats were given 30-min access intake tests with corn oil emulsions ranging in concentration from 0.125% to 64%. The volume ingested showed an inverted U shaped function over this concentration range. The Weibull function fitted to the rate of licking function showed that the initial rate of licking was an increasing linear function of the log of the concentration of corn oil. The slope of the licking rate function was an increasing curvilinear function of the log of corn oil concentration. Together these results indicate that the negative feedback effect of corn oil in the gastrointestinal tract increases more rapidly at the higher concentrations of corn oil than does its orosensory stimulating effect resulting in a decrease in the volume ingested. Unlike carbohydrates, where the increase in the initial rate of licking is a result of an increase in the size of the clusters, the increase with concentration in the initial rate of ingesting corn oil was caused by an increase in the number of clusters rather than their size. This study provides a quantitative analysis of the interaction between orosensory and postingestional stimulation, two variables that play an important role in the control of ingestion of corn oil.

Animals↗

Effect of norfloxacin on theophylline disposition: a comparison with other fluoroquinolones.

The effects of norfloxacin (NOR), at steady-state plasma concentrations of 0-32 mg.l-1, on the plasma clearance of a 6 mg.kg-1 i.v. bolus dose of theophylline (THEO) in the male Sprague-Dawley rat have been studied. The effects were characterised by a Ki value (Ki = 12 microM), which was comparable with Ki values obtained previously under identical conditions for ciprofloxacin, but higher than that obtained for enoxacin. The distributional characteristics, volume of distribution and liver to plasma concentration ratio, were very similar for the three compounds. The only marked pharmacokinetic differences were in hepatic clearance, where there was a rank order NOR > ciprofloxacin > enoxacin, a reverse of the order in the reduction of THEO clearance seen in clinical studies. The advantages of using the steady-state experimental design described here are that equivalent concentrations are utilised to compare related drugs and differences in pharmacokinetics are accounted for, to allow a direct comparison of potency. This information, together with additional pharmacokinetic considerations, suggests that the different effects on THEO clearance seen in the clinic for NOR, ciprofloxacin and enoxacin are not solely due to differences in inhibitory potency, but also involve differences in hepatic clearance and hence systemic availability of the fluoroquinolones.

Animals↗

Cholecystokinin changes the duration but not the rate of licking in vagotomized rats.

Abdominal vagotomy markedly reduces or abolishes the inhibitory effect of cholecystokinin (CCK-8) on meal size. To investigate the rate and microstructure of licking underlying this phenomenon, licking was measured throughout a meal of milk in intact and vagotomized rats after intraperitoneal injections of isotonic saline or CCK-8. CCK-8 increased the slope of the decay of licking, decreased the efficiency of licking, and decreased the duration of licking in intact rats but had no effect on either the slope of the decay of licking or the efficiency of licking, but it increased the duration of licking in vagotomized rats. These results demonstrate that abdominal vagal nerves are necessary for CCK-8 to increase the rate of decay of licking, but nonvagal mechanisms mediate the effect of CCK-8 on duration of licking.

Animals↗

Metabolism of theophylline and its inhibition by fluoroquinolones in rat hepatic microsomes.

1. The effects of beta-naphthoflavone, dexamethasone, phenobarbitone and isosafrole on the metabolism of theophylline by rat liver microsomes have been studied. Only beta-naphthoflavone, a known P4501A inducer, increased the rate of 1-methylxanthine formation (3-fold), whereas all the inducers studied increased the rate of 1,3-dimethyluric acid production (2.5-3-fold). 2. To study the effects of a range of fluoroquinolones on theophylline metabolism, beta-naphthoflavone-induced microsomes were used, as the ratio for metabolite production rates was similar to that of untreated microsomes (4:1,3-dimethyluric acid: 1-methylxanthine at 2 mM theophylline). High concentrations of fluoroquinolones (0.5-1.5 mM) were required to affect microsomal theophylline metabolism. 1-Methylxanthine was more sensitive to fluoroquinolone inhibition by enoxacin, ciprofloxacin, norfloxacin and pipemidic acid than 1,3-dimethyluric acid; CP67015, had a significant effect on 1,3-dimethyluric acid production only; binfloxacin had no effect on either pathway. 3. Ethoxycoumarin, a rapidly metabolized substrate, was also investigated as a surrogate for theophylline in in vitro experiments. Fluoroquinolone inhibition of ethoxycoumarin O-de-ethylation in beta-naphthoflavone-induced microsomes was quantitatively greater but qualitatively similar to theophylline metabolism (IC50s 440-870 microM at 2 microM 7-ethoxycoumarin). 4. These data are comparable with previous rat experiments in vivo, indicating that enoxacin, ciprofloxacin and norfloxacin have similar intrinsic activity in the inhibition of theophylline metabolism.

Animals↗

Abdominal vagotomy attenuates the inhibiting effect of mannitol on the ingestive behavior of rats.

Intact and abdominally vagotomized rats were offered for ingestion during a 30-min period a saccharin and glucose solution or another with 0.1 M mannitol added. The addition of mannitol to the test solution caused a large reduction in intake of intact rats caused by a very rapid decline in the rate of licking during the test. This did not occur with the vagotomized rats. This demonstrates that abdominal vagal nerves are necessary for the inhibitory effect of mannitol on the ingestive behavior of rats. Vagotomized rats also differed from the intact ones by ingesting less of the mannitol-free solution. This was suggested to result from accelerated gastric clearance, leading to abnormally rapid stimulation of negative feedback from the small intestine conveyed to the CNS by extravagal pathways.

Animals↗

Conditioned control of ingestive behavior by acarbose-induced inhibition of sucrose ingestion in the rat.

It has been reported that the addition of Acarbose, a alpha-glucosidase inhibitor, to a carbohydrate solution blocks a preference that otherwise would be displayed for that solution. One interpretation of those results is that the alteration in preference was caused by the diminished postabsorptive nutritive value of the diet due to the inhibition of hydrolysis of the carbohydrates, and, thus, its absorption. An alternative explanation is that the reduction in the preference was a consequence of an accumulation of undigested carbohydrates in the lumen of the intestine. In the studies reported here, designed to investigate this alternative explanation, it was shown that Acarbose added to a flavored 0.3 M sucrose solution reduced the preference for that solution in a two-bottle preference test. An analysis of the licking behavior of rats ingesting flavored 0.3 M sucrose solutions with and without the addition of Acarbose revealed that the presence of Acarbose in the test solution caused a conditioned reduction in the rate of licking the test solution at the beginning of the meal and, as a result, a reduction in intake of the solution. This conditioned control of the rate of licking was rapidly acquired and was easily reversed. It was also shown that Acarbose increased fluid retention in the small intestine, suggesting that the conditioning may have been based on the accumulation of undigested disaccharides in the intestinal lumen rather than on the diminished postabsorptive nutritive value of the ingested sucrose.(ABSTRACT TRUNCATED AT 250 WORDS)

Acarbose↗

Relationship between enoxacin and ciprofloxacin plasma concentrations and theophylline disposition.

Certain fluoroquinolone antibiotics affect theophylline (THEO) disposition by inhibition of its metabolism, yet no studies to date have investigated the relationship between fluoroquinolone plasma concentration and THEO pharmacokinetics. The effects of two fluoroquinolones, enoxacin (ENOX) and ciprofloxacin (CIPRO), have been studied in male Sprague-Dawley rats (n = 33-46) at steady state plasma concentrations of 0-33 mg.l-1, achieved by supplementing an intravenous bolus dose with a constant rate infusion. The effects of steady state ENOX and CIPRO plasma concentrations on the clearance of THEO determined after an intravenous bolus dose of 6 mg.kg-1 were described using a competitive inhibition model. The model consisted of two components, one describing a residual component of THEO clearance, which was unaffected by fluoroquinolone, the other describing the non-linear reduction of THEO clearance by fluoroquinolone. The residual clearance estimated from the model was comparable to renal clearance for THEO in the rat. The potency of each fluoroquinolone was characterised by a Ki value, the concentration reducing THEO clearance by 50% of the maximum change. These values were 4.7 microM and 16.3 microM for ENOX and CIPRO, respectively. Thus, in this study, ENOX was found to be a more potent inhibitor of THEO clearance than CIPRO. The method allowed direct in vivo comparison of potency between different fluoroquinolones, as pharmacokinetic differences, such as clearance, volume of distribution and bioavailability, were 'designed out.'

Animals↗

Abdominal vagotomy alters the structure of the ingestive behavior of rats ingesting liquid diets.

A microstructural analysis of the licking behavior of the rat was used to investigate the effects of total abdominal vagotomy on ingestive behavior. Vagotomy decreased the meal size of milk and 3 concentrations of sucrose. The decrease was due to an increase in the decline in the rate of licking during the meal, suggesting that negative feedback from the gastrointestinal tract was enhanced by vagotomy, perhaps because of accelerated clearance of fluid from the stomach to the intestine. No evidence was found for motor dysfunction of licking or alterations in gustatory sensitivity to the test solution. The results suggest that vagotomy enhanced the strength of an extravagally mediated negative feedback signal from the intestine and that the vagus nerve normally prevents this from occurring by regulating gastric clearance.

Afferent Pathways↗

Simultaneous assay of fluoroquinolones and theophylline in plasma by high-performance liquid chromatography.

A sensitive and selective reversed-phase high-performance liquid chromatographic method for the determination of theophylline in plasma simultaneously with either ciprofloxacin, enoxacin or norfloxacin has been developed. It involves extraction of plasma with chloroform-isopropanol or dichloromethane-isopropanol prior to chromatography on a Spherisorb ODS2 column. The mobile phase is 15% acetonitrile in a phosphate buffer (pH 3.0) containing tetrabutylammonium hydrogen sulphate (4.4 mM) as an ion-pairing agent. Ultraviolet detection is carried out at 280 nm. Run time is less than 10 min for all three separations. The assays have been used to determine the effect of plasma concentrations of fluoroquinolone on theophylline clearance.

Animals↗

The acquired control of ingestive behavior in the rat by flavor-associated postingestional stimulation.

Recently reported sham feeding studies have revealed that the rate of ingestion of liquid diets early in the ingestion interval is under the associative control of postingestive events occurring in the stomach and intestine. This study investigated the possibility that gastrointestinal filling induced by adding the nonabsorbable sugar alcohol mannitol to a test solution could serve as an unconditioned stimulus to support the acquired control of the initial rate of ingestion of a liquid by rats. The results revealed that mannitol had a direct unconditioned effect on the rate of decline in the rate of ingestion during the meal and that the association of it with a distinctive flavor resulted in an acquired control of the initial rate of licking conditioned to the flavor. The conditioned effect was rapidly acquired and rapidly extinguished. Our results demonstrate the preabsorptive mechano- or chemostimulation of the gastrointestinal tract can serve as a UCS to support the conditioning of the rate of ingestion early in the meal.

Animals↗

Food deprivation- and palatability-induced microstructural changes in ingestive behavior.

The effects of 17 h food deprivation and stimulation by five concentrations (0.05-0.8 M) of sucrose solutions on the licking behavior of rats were investigated. Food deprivation increased the intake of the three lowest concentrations (0.05, 0.1, and 0.2 M) but had no effect on the volume ingested of the two highest concentrations (0.4 and 0.8 M). Food deprivation had no significant effect on the duration of the meals of any of the sucrose solutions; rather it affected the rate of ingestion. In those cases where food deprivation did affect volume intake, it did so by increasing the initial rate of ingestion. Although food deprivation had no effect on the volume ingested of the two strongest concentrations of sucrose, it nevertheless affected the ingestive behavior by increasing the duration of the sustained periods of bursts of licking and decreasing their number. Deprivation also significantly decreased the rate of licking within these sustained bouts of licking. The results indicate that food deprivation can affect the ingestive behavior of rats in ways that are not revealed by measuring volumetric intake alone. The data also support the view that food deprivation increases the palatability of the test solutions.

Animals↗

Postpyloric stimuli are necessary for the normal control of meal size in real feeding and sham feeding rats.

When 0.8 M sucrose is sham fed, intake increases progressively on consecutive tests and then plateaus. Interspersing two real feeding tests between sham feeding tests prevents this increase in sham intake [J. D. Davis and G. P. Smith. Am. J. Physiol. 259 (Regulatory Integrative Comp. Physiol. 28): R1228-R1235, 1990]. This is consistent with an acquired control of ingestion based on an association between an oropharyngeal conditioned stimulus (CS) and a postingestional unconditioned stimulus (UCS). To determine if this postingestional UCS has a gastric or postgastric origin (or a combined one), we confined ingested 0.8 M sucrose to the stomach on real feeding and sham feeding tests by closing the pylorus with an inflatable Silastic cuff. Rats were tested on seven sham feeding tests separated by two real feeding tests and then on six consecutive sham feeding tests. In contrast to our previous results [Davis and Smith. Am. J. Physiol. 259 (Regulatory Integrative Comp. Physiol. 28): R1228-R1235, 1990], intake increased progressively on the real feeding and both types of sham feeding tests. We conclude that both gastric and postgastric stimuli act as a UCS for the acquired control of meal size.

Animals↗

Differential effects of serotonergic and catecholaminergic drugs on ingestive behavior.

The serotonergic agonists fenfluramine and fluoxetine and the catecholaminergic agonists amphetamine and phenylpropanolamine are well known to cause a reduction in intake in rats. In the studies reported here we investigated the effects of these drugs on the microstructure of licking behavior of the rat ingesting 0.4 M sucrose. The purpose was to examine the similarities in the behavioral effects within and between these two classes of anorectic agents. The serotonergic agonists fenfluramine and fluoxetine caused a reduction in intake primarily by reducing the size of bursts and clusters of licking within the test meal without affecting the duration of the meal, suggesting a reduction in the palatability of the test solution. The catecholamine agonists amphetamine and phenylpropanolamine reduced intake primarily by reducing the number of bursts and clusters without affecting their size, suggesting a fractionation in the organization of the normal pattern of ingestion. The differences between the two serotonin and the two catecholamine agonists on the microstructure of the licking behavior suggest a different effect of the two neurotransmitters on the motor system that controls ingestive behavior. The similarities between the two different agonists within each class suggests a common neurotransmitter mechanism responsible for these two different effects on the behavior of the animals.

Animals↗

Lack of an order effect in brief contact taste tests with closely spaced test trials.

The number of licks during 30-s exposures to a range of concentrations of sucrose, glucose, fructose, maltose, and Polycose were recorded. A complete series of concentrations of each carbohydrate was offered in ascending, descending, or random order with 30-s intertrial intervals. The order of presentation differed on different days. For sucrose, glucose, fructose, and maltose the number of licks in the 30-s periods was an increasing monotonic function of concentration regardless of the order of stimulus presentation. For Polycose, the lick rate-concentration function was an inverted U-shaped function of concentration with a peak on the 0.1 M to 0.2 M range. In all cases the rate of licking declined during the 30-s exposure period, suggesting the development of gustatory sensory adaptation. The results indicate that it is possible to obtain a rapid assessment of the taste sensitivity of the rat to a variety of carbohydrate solutions on a single day with very brief intertrial intervals.

Animals↗

The management of fixed flexion contractures during total knee arthroplasty.

Fifty-one knees in 40 patients with joint surface degeneration accompanied by fixed flexion contractures (FFC) greater than 20 degrees were treated with total knee arthroplasty using a minimally constrained posterior cruciate ligament retaining prosthesis. Special techniques were employed in an attempt to achieve maximal correction at the time of surgery. The residual FFC measured 3.1 degrees at the completion of the arthroplasty, 10.1 degrees at three months, and 7 degrees at two years. At 55 months postoperatively, the FFC for the osteoarthrotic group had improved from 25.5 degrees to 3.6 degrees, whereas the rheumatoid group improved from 28.7 degrees to 8.6 degrees. The average knee score for the osteoarthrotic group was 89 compared with 81 for the rheumatoid group. Knees that were left with greater residual FFC at the completion of the arthroplasty were found to have greater residual FFC at the latest review.

Adult↗