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PubMed2002

Outcomes research in head and neck reconstruction.

Modern management of advanced upper aerodigestive tract malignancy often results in profound effects on function and appearance. These functions include speech, deglutition, mastication, taste, oral hygiene, and airway maintenance. The most commonly studied site in the head and neck is the oromandibular complex. The primary goals of reconstruction are the preservation and restoration of these functions along with socially acceptable cosmesis. Achieving these objectives is not to be accomplished at the expense of acceptable oncologic principles. With the availability of microvascular free tissue techniques, single-stage oromandibular reconstruction is now commonly performed. Few studies, however, have critically examined the functional outcomes of these techniques. To date, these investigations have been limited and retrospective. Lack of a uniform system for reporting defect size and locations as well as patient function and quality of life has limited the utility of the available data. In this article, outcomes research in head and neck reconstruction is discussed with regard to objective study parameters using the oral cavity as a model. Pertinent current literature is cited.

Activities of Daily Living↗
PubMed1992

Antidepressant-like effects of dopamine agonists in an animal model of depression.

Chronic exposure to mild unpredictable stress (CMS) has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions. There is evidence that the effect of antidepressants in this model is mediated by an increase in transmission at dopamine (DA) synpases. The present study investigated whether another treatment known to increase the functional responsiveness of DA systems, intermittent administration of DA agonists, would have antidepressant-like effects. In three experiments in rats, CMS-induced decreases in sucrose consumption were reversed by three to four twice-weekly injections of quinpirole (100-200 micrograms/kg) or bromocriptine (2.5 mg/kg). The effects lasted for several weeks, and when they waned, could be reinstated by a single additional injection of quinpirole. As with tricyclic antidepressants, the effect of quinpirole was reversed by raclopride, administered acutely immediately prior to a sucrose consumption test; there were no changes in sucrose intake in nonstressed control animals. The results suggest that intermittent administration of DA agonists merits investigation as a novel strategy for the treatment of depression.

Animals↗
PubMed2005

Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions.

Many symptoms of human depressive disorders are also observed in animals after exposure to unpredictable stressors. The chronic mild stress (CMS) paradigm was developed in order to better model the human situation by using chronic mild stressors over a longer period. It is claimed that the model induces anhedonia in the animals, a core symptom of depression in humans. Despite the fact that the CMS model has a high degree of face validity, there are a number of laboratories in which the establishment of the model is less reliably observed. We have examined behavior (sexual activity and open field activity) together with hedonic measures (sucrose and saccharine intake) after exposure to CMS. CMS decreased male sexual activity (e.g. reduced capability to ejaculate) and increased activity in an open field test. The hedonic measures showed diverging results after CMS in our laboratory. Sucrose consumption was reduced, while saccharine consumption did not show a comparable change. It is concluded that CMS induces comparable alterations to some depression-like symptoms in humans. Saccharine consumption is not a reliable indicator of the hedonic responsiveness to CMS.

Analysis of Variance↗
PubMed2006

L-glutamate biosensor for estimation of the taste of tomato specimens.

An amperometric biosensor has been developed for measurement of Umami, or the taste based on the amount of L-glutamate, in tomato foods. The biosensor is based on an enzyme-mediator system in which L-glutamate oxidase is used for biochemical oxidation of L-glutamate and a tetrafulvalene-tetracyanoquinodimethane (TTF-TCNQ) paste, prepared from the mixture of TTF-TCNQ salt, graphite powder, and silicone oil, serves as the mediator. The limit of detection, calculated by use of a four-parameter logistic model, was 0.05 mmol L(-1), and the limit of quantification was 0.15 mmol L(-1). The correlation coefficient (R2) was 0.990 and the relative standard deviation was no more than 1% (n=5). The response time (tau (95)) was 20-50 s, depending on concentration. The repeatability of the sensor was better than 5% (n=10). The sensor developed was stable for more than ten days.

Amino Acid Oxidoreductases↗
PubMed1993

Response selection, sensitivity, and taste-test performance.

Tasters selected the odd stimulus from among sets of three samples of party dip. Two samples came from one batch, and one sample came from another batch. The physicochemical difference between the batches consisted of the presence or absence of added salt. Two different tests of discriminability were undertaken by the same subjects with the same stimuli: the triangle test and the three-alternative forced-choice (3-AFC) method. Although different numbers of correct selections were obtained in the two tasks, an index of discriminability, d', had the same value when the data were analyzed in accordance with the Thurstone-Ura and signal-detection models, respectively. The average data support Frijters's (1979b) contention that different models of the discrimination process are appropriate to the results of the triangular and the 3-AFC procedures. Further analysis of the data revealed that discrimination was poorer for trios containing one physicochemically weak stimulus and two stronger stimuli than it was for trios containing one stronger stimulus and two weak stimuli. A two-signal 3-AFC task was undertaken by some subjects, and d' estimates from this task were lower than expected on the basis of performance in the other tasks.

Adult↗
PubMed2005

A pilot study of ondansetron plus metopimazine vs. ondansetron monotherapy in children receiving highly emetogenic chemotherapy: a Bayesian randomized serial N-of-1 trials design.

GOALS OF WORK: Chemotherapy-induced nausea and vomiting is problematic in paediatric brain tumour treatment protocols which often discourage the use of corticosteroids as anti-emetics. The dopamine receptor antagonist, metopimazine, is an effective anti-emetic in combination with ondansetron in adults. The present study was designed to assess its efficacy in children with cancer, a group in which it has not been studied previously. PATIENTS AND METHODS: We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing ondansetron/metopimazine with ondansetron monotherapy in children with brain tumours receiving highly emetogenic therapy and combined the individual results using Bayesian statistical modeling. MAIN RESULTS: Ten of twelve enrolled patients completed at least one chemotherapy cycle on study (median=2.5 cycles, range 1-11). Two patients were unable to complete any cycles, and a further three patients withdrew from the study prior to completing all cycles because of an inability to tolerate the taste of the study drug. Combination therapy increased the proportion of days during which patients had no emesis (overall odds ratio=1.52, 95% credible region=0.32-6.40, probability of odds ratio>1=72%), decreased the number of emetic episodes per day (overall rate ratio=0.67, 95% credible region=0.15-3.14, probability of rate ratio<1=75%) and decreased parents' ratings of their child's distress. The drug was more effective during the delayed chemotherapy phase than the acute phase. No adverse events were attributed to metopimazine. CONCLUSIONS: Based on this pilot study, we believe that the high likelihood that metopimazine is an effective adjunct to ondansetron monotherapy suggests that this combination therapy is worthy of further study in children receiving emetogenic chemotherapy.

Antiemetics↗
PubMed1988

Sodium chloride preference is altered in a rat model of liver disease.

Rats with ligation of the common bile duct were used to study the effect of liver disease on preferences for sodium chloride solutions. Preferences for NaCl were assessed by 24-hr two-bottle choice (preference) tests in both bile duct ligated (BDL) and control animals. Bile duct ligated animals showed greater preferences for 200 and 300 mM NaCl than either free-feeding or pair-fed control animals. In rats provided with continuous access to a single concentration of 200 mM NaCl both pre- and postligation, BDL animals showed an abrupt change in NaCl preference at day 12 postligation, while control animals showed no alterations in preference during the same time period. The results provide additional support for a role of the liver in determining NaCl solution preference and suggest that the BDL rat may be a useful model for the study of altered gustatory function in liver disease.

Animals↗
PubMed2004

Effect of beta-cyclodextrin on aroma release and flavor perception.

Binding and release of volatile compounds to and from beta-cyclodextrin were measured in model aqueous systems using static equilibrium headspace and dynamic headspace dilution. Beta-cyclodextrin decreased the static equilibrium headspace for some volatiles (e.g., ethyl octanoate and decanone) due to binding, but dilution studies demonstrated that binding was readily reversible. Dynamic release of hydrophobic volatile compounds was similar to that observed from emulsions. When beta-cyclodextrin was added to fat free yogurt, the release of a commercial lemon flavoring was modified and was similar to release from a regular fat yogurt. Sensory difference testing confirmed the release results. The data demonstrate that beta-cyclodextrin can be used to modify flavor delivery in both model and real systems; the effects in the latter are sensorially significant.

Cyclodextrins↗
PubMed1990

Conformation-activity relationship of sweet molecules. Comparison of aspartame and naphthimidazolesulfonic acids.

The shape of the active site of the receptor for sweet molecules was previously defined on the basis of a combination of both rigid (saccharins) and flexible (aspartame) molds. In this paper, the sweetness receptor is refined with use of the shapes of 3-anilino-2-styryl-3H-naphtho[1,2-d]imidazolesulfonate (sweet) and of 3-anilino-2-phenyl-3H-naphtho[1,2-d]imidazolesulfonate (tasteless), two large and almost completely rigid tastants. The minimum-energy conformations of the flexible portions of these tastants have been determined by using a detailed conformational analysis based on ab initio calculations. The refined receptor site is still consistent with all previously examined sweet molecules. In order to unequivocally assign the prochiral beta-CH2 protons of the Phe moiety of aspartame, (2S,3S)-[2H]-alpha-L-Asp-L-PheOMe was synthesized and examined by 500-MHz 1H NMR spectroscopy. The results indicate that the minimum-energy conformation for aspartame in water, DMSO-d6, and CDCl3 (as a crown ether complex) is different from that originally proposed (FIIDII instead of FIDII, according to a notation referred to the side chains). Although this conformation is not directly consistent with the shape of the sweet receptor, the interconversion of FIIDII to FIDII was found to require only 1 kcal/mol. Furthermore, a 120-ps molecular dynamics simulation in vacuo confirms the high flexibility of aspartame and the accessibility of the FIDII conformer whose topology is fully consistent with our model.

Aspartame↗
PubMed2006

Lateral parabrachial lesions disrupt paraoxon-induced conditioned flavor avoidance.

Preliminary clinical evidence obtained in Gulf War veterans and patients suffering multiple chemical sensitivity points to the existence of a potential link between environmental exposure to organosphosphates (OPs) and the emergence of unspecific sickness syndromes in which associative Pavlovian conditioning might be partly involved. A laboratory animal model might be a useful tool for analyzing the involvement of conditioning in sickness syndromes potentially linked to OP poisoning. The first objective in the present study was to determine if paraoxon (PX), the neuroactive metabolite of the OP parathion, elicits a conditioned avoidance response to a novel stimulus (a taste-odor compound) in a conditioned flavor aversion procedure. Data obtained in Experiment 1 show conditioned flavor avoidance, demonstrative of the associative nature of the sickness properties of PX. The second objective was to characterize the nature of the specific physiological cue serving as the unconditioned stimulus in PX-induced conditioned avoidance. Despite PX administration did induce cholinergic hyperactivity, as measured by body hypothermia and increased jaw movements, lesions of the lateral parabrachial area (lPB) disrupted PX-elicited flavor avoidance responses, indicating that cholinergic signs were not sufficient as unconditioned stimuli supporting avoidance responses. Given that lPB neural integrity is necessary to process aversive interoceptive information, disruption of conditioned flavor avoidance as a result of lPB lesions is consistent with a central interruption of interoceptive processing in PX-poisoned animals. Data are discussed under the light of the hypothesis claiming the importance of associative processes and noncholinesterase targets in sickness syndromes potentially induced by OP exposure.

Animals↗
PubMed2000

Radiofrequency (pacing and thermic effects) in the treatment of sleep-disordered breathing.

Radiofrequency, whether it is used for pacing or for its thermal liberation properties, has been investigated as a treatment for sleep-disordered breathing. Diaphragmatic pacing has a long history. The problems associated with pacing, which are related to patient selection, equipment failure, disturbances at the electrode/nerve interface, neuromuscular function failure, muscle fatigue, and the physiological consequences of stimulation, will have to be resolved with XIIth nerve stimulation. Radiofrequency thermal ablation has been applied on the tongue of an animal model. In man, turbinates, soft palate tissue and the base of tongue have been treated. These feasibility studies have demonstrated that obstructive sleep apnea syndrome and upper airway resistance syndrome can be completely controlled using radiofrequency thermal ablation in some subjects. These results can be obtained without complications related to speech, taste or swallowing. The treatment can be administered as an outpatient procedure, but many applications are needed, and treatment may span 6 months. Too high a level of radiofrequency will cause pain or otherwise avoidable complications. The determination of which patients will benefit most from these procedures will require further multi-center, placebo-controlled studies.

Ambulatory Care↗
PubMed1996

Covert manipulation of the dietary fat to carbohydrate ratio of isoenergetically dense diets: effect on food intake in feeding men ad libitum.

OBJECTIVE: High-fat, high energy-density (HF, HED) diets promote an increase in energy intakes relative to low-fat lower-energy density diets (LF, LED). This study examined whether HF diets promote higher levels of energy intake when isoenergetically dense (IE) relative to LF (high carbohydrate) diets, as predicted by glucostatic and glycogenostatic models for energy intake regulation. SUBJECTS: Six normal-weight healthy men [mean age (SD) = 37.33 (13.32 y) mean weight = 73.03 (5.14 kg), mean height = 1.80 (0.05 m)]. DESIGN: Six men were each studied three times (factorial design) during 14-d throughout which they had ad libitum access to one of three covertly-manipulated diets. The fat, carbohydrate (CHO) and protein in each diet (as % energy) were 20:68:12, [low-fat (LF)]; 40:48:12, [medium-fat (MF)]; 60:28:12 [high-fat (HF)], with 2-d maintenance (1.4 x BMR, MF) beforehand. Within each diet every item was of the same composition and offered as a 3-d rotating menu. MEASUREMENTS: Energy and nutrient intakes, body weight, subjective pleasantness and satisfaction of the food. RESULTS: Energy intakes were 10.69, 11.02 and 10.90 MJ/d on the LF, MF and HF diets respectively. The increase in energy intake that occurred in previous studies when the energy density of the diet was increased by addition of fat was not apparent when LF, MF and HF diets were of the same energy density. CONCLUSION: Neither carbohydrate nor fat intake were tightly regulated. These data do not support an entirely glucostatic or glucogenostatic model of food intake regulation.

Adult↗
PubMed1997

The olfactory bulbectomized rat as a model of depression: an update.

The olfactory bulbectomized (OB) rat has been proposed as an animal model of depression. The following behavioural changes have been observed following bilateral olfactory bulbectomy: hyperactivity in an enclosed arena, such as the open-field; enhanced nocturnal hyperactivity in a 24-hr home cage activity monitor; deficits in memory, as shown by passive avoidance behaviour and in the Morris maze and the 8-arm radial maze; increased open arm entries in the elevated plus-maze; and changes in food motivated and conditioned taste aversion behaviour. Alterations in the noradrenergic, serotonergic, cholinergic, gamma-aminobutyric acid (GABA)ergic and glutamatergic neurotransmitter systems are also associated with olfactory bulbectomy. The variety of immune changes following olfactory bulbectomy includes reduced neutrophil phagocytosis, lymphocyte mitogenesis, lymphocyte number and negative acute phase proteins, increased leucocyte adhesiveness/aggregation, monocyte phagocytosis, neutrophil number and positive acute phase proteins. An enhanced nocturnal secretion of corticosterone is observed in OB rats, which is normally suppressed by dexamethasone. The most commonly employed behavioural indicator of antidepressant activity is attenuation of the OB-related hyperactivity in the open-field. However, many of the other behavioural, neurotransmitter and immune changes have been shown to be attenuated by chronic (but not acute) antidepressant treatment. Tricyclic antidepressants (amitriptyline, desipramine), atypical agents (mianserin), selective serotonin reuptake inhibitors (paroxetine, sertraline, fluvoxamine), reversible inhibitors of monoamine oxidase A (moclobemide), as well as putative antidepressants such as 5-hydroxytryptamine1A agonists (zalospirone, ipsapirone), noncompetitive N-methyl-D-aspartate antagonists (MK-801) and triazolobenzodiazepines (alprazolam, adinazolam), have demonstrated antidepressant-like activity in this model. As many of the changes exhibited by the OB rat are qualitatively similar to those observed in depressed patients, it may be concluded that the OB rat is a model of depression and not just a means whereby putative antidepressants may be tested.

Animals↗
PubMed1998

NPY and food intake: discrepancies in the model.

The evidence that NPY is an endogenous neurotransmitter that modulates both sides of the energy equation is clear and compelling. While agreeing with this (and indeed contributing to the growing literature supporting the concept), we have found that the interpretation of the increased food intake stimulated by intraventricular (i.v.t.) NPY is more complex than first appears. We discuss evidence suggesting that NPY additionally (and presumably at other receptor populations in the brain) causes sensations that produce aversion or illness. Specifically, the i.v.t. administration of NPY at doses that stimulate eating also cause the formation of a conditioned taste aversion and the animal engages in a form of pica behavior (kaolin consumption). It also suppresses an otherwise robust increase of sodium consumption. We discuss evidence suggesting that whereas NPY activates feeding behavior by stimulating the complex sequence of behaviors beginning with the seeking and finding of food and ending with food ingestion, NPY does not stimulate increased eating in the absence of the anticipatory preliminary behaviors. Finally, we briefly review evidence suggesting that whatever sensation is aroused by i.v.t. NPY, it is not necessarily the same sensation that is aroused when animals are food-deprived. Hence, one must be cautious in interpreting NPY as solely an orexigen.

Animals↗
PubMed1985

Morphine and clonidine oral self-administration: a study in morphine dependent or abstinent rats.

The ability of morphine and of clonidine to support self-administration has been evaluated in morphine dependent or abstinent rats, using an orally reinforced operant technique (F.R. 20). It was found that: Morphine drinking can function as a reinforcer of an operant response both in dependent and abstinent rats. The bitter taste of morphine becomes a secondary reinforcer for rats usually working for the alkaloid. Clonidine supports oral self-administration in morphine abstinent, but not in morphine dependent rats. The data are in line with clinical findings and give a further evidence that oral self administration in rats can be an useful model for the analysis of drug dependence.

Animals↗
PubMed2002

The need to feed: homeostatic and hedonic control of eating.

Feeding provides substrate for energy metabolism, which is vital to the survival of every living animal and therefore is subject to intense regulation by brain homeostatic and hedonic systems. Over the last decade, our understanding of the circuits and molecules involved in this process has changed dramatically, in large part due to the availability of animal models with genetic lesions. In this review, we examine the role played in homeostatic regulation of feeding by systemic mediators such as leptin and ghrelin, which act on brain systems utilizing neuropeptide Y, agouti-related peptide, melanocortins, orexins, and melanin concentrating hormone, among other mediators. We also examine the mechanisms for taste and reward systems that provide food with its intrinsically reinforcing properties and explore the links between the homeostatic and hedonic systems that ensure intake of adequate nutrition.

Animals↗