Seven men were studied during 30 minutes of leg ergometer cycling at approximately 70% V02 max to determine the effects of caffeine ingestion on the utilization of muscle glycogen. A caffeine solution (250 ml; 5 mg/kg body weight) given one hour prior to exercise (CAF trial), decreased the rate of muscle glycogen depletion by 36 + 11.86% (p. .005) as compared to a decaffeinated control trial. During the CAF treatment, there was a 16% increase in serum FFA prior to exercise. Exercise resulted in a removal of FFA from the blood in both trials. Muscle triglyceride levels prior to exercise in the CAF trial were nearly 23% higher than control levels and suggest, that excess FFA present prior to exercise in the CAF trial were esterified into triglyceride. Subsequent post-exercise values indicated a greater utilization of endogenous lipid. A model based on caffeine's stimulatory effects on muscle lipid mobilization and its inhibitory action on muscle phosphorylase a appears to be responsible for the lessened use of muscle glycogen.

The work in this dissertation aims to describe a simple new test for odor-recognition memory in rats that can be readily performed and results in an easily observable and lasting form of memory. This test has allowed for the demonstration of ethanol-induced retrograde memory impairments in rats when ethanol is administered during both the consolidation and reconsolidation phases of memory encoding. The observation that a high-dose of ethanol can cause retrograde memory impairments when administered immediately or within hours after learning has taken place is an original finding that may have implications for understanding human blackouts. Furthermore, the finding that ethanol can disrupt the reconsolidation of a previously consolidated memory has not been previously established. It is also demonstrated that caffeine can prevent ethanol’s memory impairing effects, a result that contributes a new piece of evidence for caffeine’s effects on the learning and memory process. This effect has been further investigated mechanistically and attributed to caffeine’s dual role as a phosphodiesterase type 5 inhibitor and adenosine A2A antagonist. Neither of these mechanisms alone appear to be sufficient enough to prevent the retrograde memory impairments seen with ethanol. It is hoped that this test and our findings will prove useful for future investigations into the effects of ethanol on learning and memory and the human phenomenon of alcohol-induced blackouts. / text

The present investigation was designed to elucidate the potential influence of age on speech breathing. Toward this end, 30 men representing three widely different age groups (25, 50, and 75 years) were studied. These individuals were carefully selected to meet stringent criteria, the most important of which related to health and physical characteristics. Speech breathing was studied via anteroposterior diameter changes of the rib cage and abdomen. Recordings were made during extemporaneous speaking and reading and during the performance of various chest wall maneuvers used in the measurement of the speech breathing data. In addition to speech breathing, selected measures of general respiratory function were obtained. These included measures of subdivisions of the lung volume and measures of resting tidal breathing. Results indicated that these 30 subjects were representative of other subjects studied with respect to measures of general respiratory function. Subdivisions of the lung volume were found to differ with age in the manner predicted by previous investigations. Age-related differences were most marked for measures of vital capacity and residual volume. By contrast, there were no age-related differences for measures of resting tidal breathing. Several speech breathing measures were found to differ with age. Age-related differences were usually between the 25- and 75-year-old subject groups and less commonly between the 25- and 50-year-old subject groups. For extemporaneous speaking, differences were found for lung volume excursion, rib cage volume initiation (referenced to the rib cage volume associated with the relaxed configuration of the chest wall), number of syllables per breath group, and lung volume expended per syllable (in percent vital capacity). For reading, differences were found for lung volume expended per syllable (in percent vital capacity). Age-related similarities and differences in general respiratory function and speech breathing are discussed in relation to possible underlying mechanisms. In addition, implications are drawn regarding evaluation and management of individuals with speech breathing disorders.

No description available.

Part I. In order to determine the effect of dose size on the bioavailability of phenytoin (Dilantinᴿ), a single intravenous dose of 15 mg/kg, single oral doses of 400, 800, 1600 mg, and 1600 mg in divided doses (i.e. 400 mg every three hours) were administered to six healthy male subjects. Values of V(max) and K(m) obtained from the intravenous dose were used to determine the extent of absorption from the oral doses. Although no statistically significant difference in extent of phenytoin absorption was observed, the time to reach maximum phenytoin serum concentrations increased significantly from 8.4 hours for the 400 mg dose and 13.2 hours for the 800 mg dose to 31.5 hours for the 1600 mg dose. Peak serum concentrations of 3.9, 5.7, 10.7, and 15.3 mg/1 were observed after the 400, 800, 1600 and 1600 mg divided doses, respectively. It is suggested that the prolonged, but complete, absorption of large phenytoin doses is due to a slow dissolution and continued absorption from the colon. Owing to the prolonged absorption of phenytoin, it may be necessary to use a larger oral than intravenous loading dose to produce similar maximum phenytoin serum concentrations. Part II. The effects of age and obesity on the pharmacokinetics of thiopental were studied in 7 morbidly obese (aged 25 to 46 years) and 22 lean patients (aged 25 to 83 years), who were primarily undergoing abdominal surgery. In all 29 patients, serum thiopental concentrations were determined by gas-liquid chromatography using a nitrogen-selective detector. Based upon total (bound+free) thiopental concentrations, the average (±S.E.) volumes of distribution (Vᵦ and V(ss)) were significantly larger in the obese (7.94 ± 1.72 1/kg and 4.72 ± 1.03 1/kg, respectively) than in the age-matched lean patients (1.95 ± 0.22 1/kg and 1.40 ± 0.16 1/kg, respectively). Clearance based on total thiopental concentrations normalized to total body weight (TBW) was not significantly different between the obese (0.18 ± 0.03 1/hr/kg) and lean patients (0.21 ± 0.02 1/hr/kg). However, total body clearance not normalized to TBW was significantly larger in the obese (24.98 ± 5.62 1/hr) than in the lean patients (11.86 ± 1.29 1/hr). The half-life of thiopental was significantly larger in the obese (31.87 ± 4.53 hours) than in the lean patients (6.61 ± 0.52 hours) and was primarily a function of the larger apparent volume of distribution for thiopental. The unbound fraction of thiopental in serum (range, 17.8% to 27.6%) did not depend on the degree of obesity, but was found to be greater with advancing age. The apparent volumes of distribution, Vᵦ and V(ss), were also related to age. No significant relationship was found between total body clearance with increasing age. Thus, the half-life of thiopental was positively correlated with age, and as in the obese study, was found to be primarily influenced by the apparent volume of distribution.

No description available.

The aim of these experiments was to investigate learning and memory extensively in two nonverbal domains (olfactory and visual), and to determine similarities and differences in the function of the neural substrates that subserve these modalities. Two complementary methodological approaches were taken: (1) examination of learning and retention in patients with resection from left (LR) or right (RR) temporal lobe, and (2) study of brain function via Positron Emission Tomography (PET) of healthy subjects during memory processing. / Two parallel recognition tests were developed (one olfactory, one visual) that examined memory at three stages: following a single exposure to test stimuli, after four exposures, and following a 24hr delay interval. In the olfactory patient study, LR and RR groups performed significantly worse than the healthy control subjects, with no difference between the patient groups; thus suggesting a lack of hemispheric superiority for this task. The PET study of healthy individuals supported the bilateral participation of piriform cortex during olfactory recognition. The results from these two studies, along with findings from animal work, suggest that the piriform cortices may play a role in odor memory processing, not simply in perception. / On the face memory task, LR and RR patients showed different results. Only RR patients were impaired, while LR patients did not perform differently from controls. This unique face learning paradigm was sensitive to right temporal lobe damage, and correctly classified patients by side of resection with a sensitivity rate of 82% and specificity rate of 79%, suggesting its possible utility as a clinical tool. PET face memory findings indicated greater participation of fusiform regions during long-term recognition, and greater right prefrontal activity during short-term recognition, when these conditions are directly compared to each other. / Finally, PET was used to study the same healthy subjects performing parallel odor and face working-memory tasks, focusing on regions previously shown to be important for working memory. Results revealed similar regions of activation in dorsolateral prefrontal cortex in the two modalities. This indicates an overlap in the brain regions that process olfactory and visual information when the same cognitive manipulations are being carried out online.

No description available.

No description available.

Previous studies in our laboratory have indicated that anesthetic block of neural activity at discrete sites within the limbic system, including the lateral hypothalamus and anterior cingulum bundle, causes a significant long-lasting analgesia during the formalin test. In this experiment, the local anesthetic lidocaine was microinjected into the dentate region of the hippocampus, an important limbic structure presumed to subserve the affective-motivational aspects of pain. The dentate gyrus is strategically situated at a point of convergence of widespread polysensory cortical input to the hippocampus, to allow modulation of cortical signals before they diverge into numerous limbic circuits. The results indicate that anesthetic block of the anterior region of the dentate gyrus produces analgesia in the rat during the formalin test. The analgesia produced by this procedure became apparent 30 minutes after regional block contralateral to the site of injury and persisted for the duration of the test period. These data provide further evidence that limbic forebrain structures are involved in pain and analgesia.