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PubMed1989

A randomized, controlled dose response study of intravenous sodium diethyldithiocarbamate in patients with advanced human immunodeficiency virus infection.

Sodium diethyldithiocarbamate (Imuthiol, DTC) has previously been observed to promote T-cell maturation in animal models and to reduce lymphadenopathy and improve survival in a murine AIDS model. In addition, several clinical studies have suggested that one dosage regimen may be active in patients with HIV infection. We conducted a randomized, controlled dose response study of intravenous DTC in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). Drug associated toxicities included gastrointestinal upset, burning at the infusion site, metallic taste, sneezing, confusional states, hyperactivity, delusional thinking, and myoclonus. Toxicity was ameliorated by dose reduction. The maximally tolerated dose varied for individual patients from 200 mg/m2 weekly to 800 mg/m2 twice weekly. No myelosuppression was observed. In patients with greater than 200 CD4+ cells/uL, a statistically significant reduction of lymphadenopathy occurred; whereas no beneficial effects were observed in patients with less than 200 CD4+ cells/uL. Improvement in symptom score and stabilization of CD4+ count also occurred in the treated group, although these trends did not reach statistical significance. Further controlled clinical trials of DTC in earlier HIV infection are warranted.

AIDS-Related Complex↗
PubMedDate not supplied

Side-specificity of olfactory learning in the honeybee: US input side.

In honeybees, Apis mellifera L., the proboscis extension reflex (PER) can be conditioned by associating an odor stimulus (CS) with a sucrose reward (US). As the neural structures involved in the detection and integration of CS and US are bilaterally symmetrical in the bee brain, we ask what respective role each brain side plays in the conditioning process. More specifically, the US normally used in conditioning experiments is the compound stimulation of the antennae (which triggers the PER) and of the proboscis (where bees lick the sucrose solution). Anatomically, the brain receives unilateral US input through each antenna, but bilateral input from the proboscis. By controlling each US component, we show that an antenna-US produces unilateral sensitization, whereas a proboscis-US or a compound-US induces bilateral sensitization. Bees can learn a unilateral odor CS with all three USs, but when a proboscis-US is used, new learning is inhibited on the contralateral side, owing to a possible US-preexposure effect. Furthermore, we show that the antenna-US induces both unilateral and bilateral reinforcement processes, whereas the proboscis-US produces only bilateral effects. Based on these data, we propose a functional model of the role of each brain side in processing lateralized CSs and USs in olfactory learning in honeybees.

Animals↗
PubMed1990

Repeatability of the acetylene rebreathing method in measuring cardiac output: influence of acetylene concentration.

The acetylene rebreathing method is a reliable noninvasive method for estimation of cardiac output. However, the method is not commonly used for clinical purposes. This is due mainly to the fact that acetylene is explosive at concentrations above 2% and that acetylene at concentrations above 0.5% has an unpleasant taste. In the present study we have investigated whether it is possible to reduce the concentration of acetylene to 0.3% in the rebreathing bag without degrading the repeatability of the estimated cardiac output. The problem was elucidated theoretically and experimentally. A theoretical investigation was carried out by producing an acetylene rebreathing curve from a single alveolus lung model. The theoretical study showed that the random noise arising from the gas analyzer gives rise to less than 10% of the total variation of the estimated cardiac output. The results of the experimental study showed that it is possible to reduce the acetylene concentration to 0.3% without decreasing the reproducibility of the acetylene rebreathing method.

Acetylene↗
PubMed1991

Comparison of Kaopectate with barium for negative and positive enteric contrast at MR imaging.

In an evaluation of safe, inexpensive, orally administered contrast agents for use at magnetic resonance imaging, different concentrations of the clay agents kaolin-pectate and attapulgite were compared in an in vitro phantom by performing spin-echo imaging with variable echo times to estimate T2 relaxation time. Additional phantoms containing from 0% to 100% attapulgite or barium preparations were compared by using spin-echo and spoiled-gradient-echo techniques to estimate T1, T2, and T2* relaxation times. In vivo spin-echo and gradient-echo images were obtained of 10 healthy volunteers and of five patients with pancreatic disease after oral administration of 12-16 oz of attapulgite preparation. T1 and T2 relaxation times obtained with use of attapulgite were slightly lower than those obtained with kaolin-pectate at both 50% and 25% concentrations. Compared with barium, attapulgite had shorter T1, T2, and T2* relaxation times, and concentration-dependent relaxivity was greater by nearly an order of magnitude. All subjects were able to drink the attapulgite, and the only complaints were of bad taste and mildly loose stools.

Barium Sulfate↗
PubMedDate not supplied

Learned immunosuppression is associated with an increased risk of chemically-induced tumors.

Based on the hypothesis that certain aspects of the CNS and immune system interact and that altered immune function affects carcinogenesis, an animal model was developed to examine the effects of learned immunosuppression on the development of a chemically induced tumor. In two experiments, we evaluated whether mice, for which immunosuppression was associated with a neutral (conditioned) stimulus, would exhibit an increased susceptibility to tumor development upon reexposure to the conditioned stimulus, as compared to nonconditioned and control animals. A taste aversion conditioning paradigm, based on classical conditioning techniques, was employed to suppress immune function using the cytotoxic and immunosuppressive drug cyclophosphamide (CY) as the unconditioned stimulus and consequently increase the risk of chemically induced tumorigenesis. CY (100 mg/kg, intraperitoneal) was paired with saccharin in the drinking water (0.1%) of adult female mice (CF-1). Conditioned mice were exposed to saccharin twice in the absence of CY, on days 4 and 7 after the first exposure (day 1). All mice were injected with the chemical carcinogen 9,10-dimethylbenzanthracene (DMBA, 50 mg/kg, subcutaneous) on day 4 of conditioning. Two subsequent exposures to saccharin alone substantially increased the risk of developing DMBA-induced tumors (ranging from 83-91%), as compared to control animals (36%) that had not received this pairing. Mice that received all agents (i.e., CY, DMBA, and saccharin) in a slightly different order did not display elevated tumor incidence. Three separate exposures to CY also significantly increased the number of animals developing tumors in response to the carcinogen (75%). Mice were observed for at least 8 weeks after conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Preference gives more consistent judgments than oddity only if the task can be modeled as forced choice.

Earlier data showed that subjects presented with two samples of distilled water and one of tap water were significantly more consistent in choosing the tap water as preferred than in identifying it as the odd sample in the set. The results were sometimes interpreted as demonstrating greater sensitivity for hedonic judgments than for oddity judgments. They are now shown to be explained by the statistical properties of the decision rules followed in different judgment tasks. In a new experiment, oddity and preference judgements were obtained in a replication of the original task with extra conditions. In two of the new conditions, the decision structure of a preference task was the same as that for the oddity task; in these conditions, performance was no better than with explicit oddity responses. The Thurstone-Ura model of triangle judgments proposed by Frijters predicts the results as an outcome of the greater statistical power of three-alternative forced choice tests compared with triangular tests. An excellent fit to all the data is given by a model wherein all subjects have the same d' for the difference between the water types but 25% of them prefer distilled water to tap water.

Choice Behavior↗
PubMed1971

Peripheral interactions among single papilla inputs to gustatory nerve fibers.

Recordings were made from single fibers of the rat chorda tympani nerve while the peripheral receptor fields were mapped using a stimulator developed to stimulate single fungiform papillae which in the rat contain a solitary taste bud. The results indicate that several fungiform papillae may supply input to a single fiber, and the most sensitive papilla of these provided, on the average, about one-half of the response of that fiber to stimulation of the entire tongue. The magnitude of the response to each concentration of stimulus and the shape of the concentration-response curves differ among papillae innervated by the same fiber. If one of the papillae supplying input to the fiber was stimulated individually with NaCl solution, application of this stimulus to the tongue surface surrounding the isolated papilla resulted in enhancement of the fiber response. If the papilla was stimulated with NaCl and potassium benzoate solution was applied to the surround, a depression of the response occurred. The excitatory input of the cationic stimuli and the depressing influence of the anionic stimuli interacted to determine the resultant steady-state impulse frequency of the single afferent fiber. A hypothetical model involving the summation of generator currents along the unmyelinated terminals of the single afferent neuron is presented as a speculative explanation of the integration of inputs from several receptors innervated by the same single fiber.

Action Potentials↗
PubMed2006

Citalopram counteracts depressive-like symptoms evoked by chronic social stress in rats.

Recently, we have described a new model of chronic social stress in rats, based on the resident-intruder paradigm. In this model, rats show behavioural changes that may be considered correlates of depressive symptoms, such as anhedonia and motivational deficits. The present study was designed for pharmacological validation of this model. Animals were socially stressed for 5 weeks and, in parallel, after the first week of stress, they were subjected to chronic (4 weeks) treatment with the antidepressant drug citalopram. The drug was administered via drinking water (30 mg/kg). The optimal dose of citalopram was determined in a pilot study. After 4 weeks of treatment, plasma levels of citalopram and its metabolite were found to be within the human therapeutic range. The effects of social stress and citalopram treatment were assessed by behavioural tests. Chronically stressed rats showed reduced locomotor and exploratory activity, reduced sucrose preference and increased immobility time in the forced swimming test. Chronic oral administration of citalopram abolished those effects and normalized behaviours related to motivation and reward sensitivity. These observations provide evidence for the predictive validity of the chronic social stress paradigm as a model of depressive symptoms in rats.

Administration, Oral↗
PubMed2002

Immunoreactivity against choline acetyltransferase, gamma-aminobutyric acid, histamine, octopamine, and serotonin in the larval chemosensory system of Dosophila melanogaster.

We have studied the distribution of choline acetyltransferase (ChAT), gamma-aminobutyric acid (GABA), histamine, octopamine and serotonin in the larval chemosensory system of Drosophila melanogaster. Colocalization at the confocal level with green fluorescent protein (GFP) or Tau-GFP reporters, expressed in selected P[GAL4] enhancer trap lines, was used to identify the cells making up these neurotransmitters. As in the adult fly, larval olfactory afferents project into the (larval) antennal lobe (LAL), where they synapse onto local interneurons and projection neurons, whereas gustatory afferents terminate essentially in the tritocerebral-subesophageal (TR-SOG) region. We demonstrate that the neuropils of the LAL and the TR-SOG are immunoreactive to ChAT and GABA. In addition, serotonin- and octopamine-immunoreactive fibers are present in the LAL. ChAT immunostaining is localized in subsets of olfactory and gustatory afferents and in many of the projection neurons. In contrast, GABA is expressed in most, and perhaps all, of the local interneurons. Serotonin immunoreactivity in the LAL derives from a single neuron that is situated close to the LAL and projects to additional neuropil regions. Taken together, these findings resemble the situation in the adult fly. Hence, given the highly reduced numbers of odorant receptor neurons in the larva, as shown in a previous study (Python and Stocker [2002] J. Comp. Neurol. 445:374-387), the larval system may become an attractive model system for studying the roles of neurotransmitters in olfactory processing.

Animals↗
PubMed2006

Intensity and persistence profiles of flavor compounds in synthetic solutions. Simple model for explaining the intensity and persistence of their aftersmell.

Hydroalcoholic solutions containing a single aroma-active compound were evaluated by a sensory panel to determine the difference between ortho and retronasal odor intensities (DeltaI(ro)), buccal savoring, and aftersmell duration. Eight compounds were used. Buccal perception seems to be just a physiologically restricted form of retronasal perception. DeltaI(ro) values were dependent on the panel, although results from the two panels were significantly correlated. Such differences and the aftersmell persistence were also significantly correlated with different physicochemical parameters related to volatility. A simple model to explain such dependence is proposed. The model considers the mouth-throat system as a perfect mixing tank with a finite amount of odorants being progressively diluted by swallowing and purging (both taken as continuous processes). Retronasal intensity is modeled from the odor properties of the liquid in such a tank calculated from orthonasal odor intensity versus concentration (I/log C) curves. The model explains successfully experimental results and has also been successfully applied to instrumental data from other authors.

Alcohols↗
PubMed2005

Odor-active constituents in fresh pineapple (Ananas comosus [L.] Merr.) by quantitative and sensory evaluation.

By application of aroma extract dilution analysis (AEDA) to an aroma distillate prepared from fresh pineapple using solvent-assisted flavor evaporation (SAFE), 29 odor-active compounds were detected in the flavor dilution (FD) factor range of 2 to 4,096. Quantitative measurements performed by stable isotope dilution assays (SIDA) and a calculation of odor activity values (OAVs) of 12 selected odorants revealed the following compounds as key odorants in fresh pineapple flavor: 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDF; sweet, pineapple-like, caramel-like), ethyl 2-methylpropanoate (fruity), ethyl 2-methylbutanoate (fruity) followed by methyl 2-methylbutanoate (fruity, apple-like) and 1-(E,Z)-3,5-undecatriene (fresh, pineapple-like). A mixture of these 12 odorants in concentrations equal to those in the fresh pineapple resulted in an odor profile similar to that of the fresh juice. Furthermore, the results of omission tests using the model mixture showed that HDF and ethyl 2-methylbutanoate are character impact odorants in fresh pineapple.

Ananas↗
PubMed2003

Susceptibility to amphetamine-induced place preference is predicted by locomotor response to novelty and amphetamine in the mouse.

RATIONALE: It has been demonstrated that major differences between mice of the C57BL/6J and DBA/2J inbred strains for amphetamine-induced place conditioning (preference and avoidance, respectively) are evident in standard housing conditions but abolished by temporary restricted feeding. This gene-experience model may be usefully exploited to dissect behavioral phenotypes related to place conditioning induced by addictive drugs. OBJECTIVES: This study evaluated a number of behavioral phenotypes related to amphetamine-induced place preference for strain differences (C57BL/6J vs DBA/2J) susceptible to be abolished by temporary food restriction. METHODS: Mice of the two inbred strains were tested for: (1) conditioned taste aversion and place preference induced by amphetamine within the same dose-range; (2) preference for a novel compartment 24 h after a single exposure to only one of two compartments; (3) amphetamine-induced behavioral sensitization and conditioned hyperactivity; and (4) locomotor activity during exploration of a novel environment. RESULTS: The two strains showed consistent taste aversion at doses of amphetamine that promoted opposite strain-dependent place conditioning. Both strains spent more time exploring the novel rather than the known compartment of the place conditioning apparatus. Instead, only mice of the C57 strain showed amphetamine-induced behavioral sensitization and conditioned hyperactivity. However, temporary food restriction did not affect strain differences for these phenotypes. Finally, C57 mice were more active than DBA in a novel environment and restricted feeding abolished this strain-dependent difference. CONCLUSIONS: These results relate individual differences for amphetamine-induced place conditioning with locomotor response to amphetamine and novelty.

Amphetamine↗
PubMed2001

The application of powdered activated carbon for MIB and geosmin removal: predicting PAC doses in four raw waters.

Blooms of blue-green algae in reservoirs often produce the musty-earthy taste and odour algal metabolites 2-methylisoborneol (MIB) and geosmin. MIB and geosmin are not removed by conventional water treatment and their presence in the distribution system, even at low ng L-1 levels, can result in consumer complaints. Powdered activated carbon (PAC) can effectively remove MIB and geosmin when the correct dose is applied. The homogeneous surface diffusion model (HSDM) was used to predict PAC doses required to reduce MIB and geosmin concentrations to below 10 ng L-1 at four water treatment plants in Adelaide, South Australia. In jar tests, undertaken under treatment plant conditions, the predicted doses were found to produce water of the desired quality in three of the four waters. The poor predictions found in the fourth water, which had a considerably higher turbidity, were attributed to the incorporation of PAC in a larger, denser floc, leading to a reduced effective contact time of the adsorbent. It was found that higher doses of PAC were required for both compounds to produce acceptable quality water when turbidities rose above 26 NTU.

Adsorption↗
PubMed1995

Intravenous caffeine in stimulant drug abusers: subjective reports and physiological effects.

The present study was conducted to examine the self-reported (i.e., subjective) and physiological effects of intravenous caffeine in 10 subjects with histories of stimulant drug abuse. Under double-blind conditions, subjects received each dose of caffeine (0, 37.5, 75, 150 or 300 mg/70 kg) twice according to a latin-square design; injections were 10 sec in duration and separated by at least 24 hr. Effects were measured before injection and repeatedly afterward for 60 min. Caffeine dose-dependently increased ratings of positive mood (e.g., increased ratings of drug liking and high), which peaked at 2 min after injection and progressively decreased. Caffeine also dose-dependently increased the frequency of stimulant identifications on the Pharmacological Class Identification Questionnaire (e.g., like cocaine, amphetamine). Caffeine also produced negative-mood effects (e.g., increased ratings of bad effects) and increases in self-reported desire for cocaine. In contrast to the positive-mood effects, the negative-mood effects were of smaller magnitude and only significant at the highest dose. Caffeine increased reports of unusual smells and tastes. Caffeine decreased heart rate (7 bpm) and skin temperature (4 degrees C), and increased systolic and diastolic blood pressures (8 and 6 mm Hg, respectively). The mood effects but not the physiological effects of intravenous caffeine were similar to those previously observed with cocaine in studies using similar methods and subjects. Intravenous caffeine administration may provide a useful model system for investigating factors relevant to the use and abuse of stimulant drugs.

Adult↗
PubMed1997

Neural responses to bitter compounds in rats.

To determine whether the idiosyncratic distribution of transduction mechanisms for bitter tastants in rat taste receptor cells (TRCs) could be inferred from the neural activity they evoke, single neuron responses to ten bitter-tasting compounds were recorded from rat glossopharyngeal (n = 30) and chorda tympani (n = 22) neurons. Responses to several 'bitter' alkaloids were obtained: 10 mM quinine-HCl, 50 mM caffeine, and 1 mM each nicotine, yohimbine, and strychnine, plus a number of non-alkaloid bitter-tasting compounds: 0.1 M KCl, 0.01 M MgCl2, and 1 mM each phenylthiocarbamide (PTC), L-tyrosine, and denatonium benzoate. To obtain some distinctions with other stimuli NaCl (0.1 M), HCl (pH 2.0), and capsaicin (10 microM) were also tested. It was found that individual neurons in both glossopharyngeal and chorda tympani nerves differed in their relative sensitivities to the various bitter stimuli. To determine relationships among these stimuli, the differences in the evoked responses between each stimulus pair were summarized in a multi-dimensional scaling space. In these analyses neither nerve showed any obvious similarity between the placements of quinine and the other bitter stimuli. Such data suggest that first-order gustatory neurons can discriminate among the above bitter stimuli. For glossopharyngeal neurons, some similarity to quinine was found only for nicotine and denatonium, and for chorda tympani neurons, some similarity to quinine was found only for KCl and MgCl2. Of the bitter compounds tested, quinine evoked the greatest response from glossopharyngeal neurons. We propose this arises because quinine can activate TRCs by more transduction mechanisms than other bitter stimuli. The results from these studies were summarized in a qualitative model for the coding of bitter tastants where the variety of transduction mechanisms for bitters are distributed among various TRCs to account for the heterogeneous responses among the neurons.

Animals↗
PubMed1997

Conditioned immunosuppression of lipopolysaccharide-induced antibody response of orally immunized mice.

BALB/C mice previously conditioned in a paired regimen in which cycophosphamide was given in association with a novel taste in the drinking water (saccharin, SAC) subsequently received LPS (1mg/mouse) by oral gavage. Subgroups of mice were reexposed to SAC or water respectively, and anti-LPS antibody production measured 6 days later using an ELISA/ELISPOT assay. Our data show that the immune response to this T-independent antigen, administered orally, is amenable to conditioned immunosuppression in this model system.

Administration, Oral↗
PubMed2001

Conditioned food aversion in Suncus murinus (house musk shrew) - a new model for the study of nausea in a species with an emetic reflex.

The lack of a small animal model with an emetic reflex in which the relationship between conditioned food aversion and emesis could be investigated prompted a study of the insectivore, Suncus murinus (the house musk shrew). A novel food (either tuna or chicken cat food) was paired (C+) with a single exposure to either nicotine (4 mg/kg sc), motion (1 Hz, 4 cm, 10 min) or lithium chloride (100 mg/kg ip) or was paired (C-) with either saline or sham exposure to motion. Nicotine and motion both induced emesis (retching/vomiting) but lithium chloride did not. All three treatments produced a conditioned food aversion after a single pairing with consumption of C+ food. When given a choice between the two foods, S. murinus given lithium chloride, motion exposure and nicotine consumed, respectively, only 25%, 23% and 1% of their total intake from the C+ food. This study shows that a conditioned food aversion can be readily induced in S. murinus and that the induction of emesis can be uncoupled from food aversion. S. murinus provides a promising new model in which the relationship between emesis, nausea and conditioned food aversion can be investigated.

Animals↗
PubMedDate not supplied

Differences in salivation to repeated food cues in obese and nonobese women.

In a series of studies we have shown that salivation, a cephalic phase preingestive response, habituates to repeated presentations of olfactory or gustatory cues in nonobese subjects. Previous research has studied the differences in anticipatory response to food cues in obese vs. nonobese subjects. This study was designed to assess if obese and nonobese females differed in their patterns of salivary response to repeated presentation of palatable food cues. The salivary response to 10 gustatory presentations of lemon yogurt was studied in 10 obese and 10 nonobese nonrestrained women. Results showed significant differences in the pattern of salivary responding, with obese subjects showing a significantly slower decline in salivation than nonobese subjects. These results are consistent with the hypothesis that obese women differ from nonobese women in their pattern of response to repeated food cues. The results are discussed in relationship to models of intake that focus on differences in satiety or differences in the reinforcing value of food between obese and nonobese subjects.

Adolescent↗