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PubMedDate not supplied

Gamma-hydroxybutyric acid versus alcohol preference in Sardinian alcohol-preferring rats.

Previous experiments demonstrated that the selectively bred Sardinian alcohol-preferring (sP) rats possess a genetically based proclivity to consume pharmacologically relevant doses of gamma-hydroxybutyric acid (GHB). The present study was aimed at comparing the reinforcing properties of GHB and ethanol, measuring the propensity of sP rats to consume GHB and ethanol when both drugs were concomitantly available. Initially, two groups of sP rats (ethanol-naive and ethanol-experienced, respectively) were forced to consume GHB in order to help them discover the reinforcing properties, which could then prevail over the unpleasant taste of the GHB solution. Subsequently GHB (at concentrations increasing from 1 to 6% w/v) was offered in free choice with water and all rats consumed pharmacologically relevant amounts of GHB. Finally, under the free-choice regimen between GHB (presented to each rat at its preferred concentration), ethanol and water, daily ethanol intake averaged approximately 6 g/kg (i.e. the amount of ethanol usually consumed by sP rats), whereas GHB intake declined by approximately 75%. In the few rats showing a high intake of GHB, ethanol intake was not altered. No difference in GHB drinking behaviour was ever recorded between ethanol-naive and ethanol-experienced rats. The results of the present study demonstrate that freely available GHB is not capable of altering ethanol preference and consumption in sP rats and suggest that the postulated reciprocal substitutability of the two drugs does not completely include the reinforcing properties, at least in sP rats and when oral self-administration of GHB is considered. The results also provide a model of the low abuse liability of GHB observed in human alcoholics.

Alcohol Drinking↗
PubMed2006

The neurocognitive bases of human multimodal food perception: consciousness.

This review explores how we become aware of the (integrated) flavor of food. In recent years, progress has been made understanding the neural correlates of consciousness. Experimental and computational data have been largely based on the visual system. Contemporary neurobiological frameworks of consciousness are reviewed, concluding that neural reverberation among forward- and back-projecting neural ensembles across brain areas is a common theme. In an attempt to extrapolate these concepts to the oral-sensory and olfactory systems involved with multimodal flavor perception, the integration of the sensory information of which into a flavor gestalt has been reviewed elsewhere (Verhagen, J.V., Engelen, L., 2006. The neurocognitive bases of human multimodal food perception: Sensory integration. Neurosci. Biobehav. Rev. 30(5): 613_650), I reconceptualize the flavor-sensory system by integrating it into a larger neural system termed the Homeostatic Interoceptive System (HIS). This system consists of an oral (taste, oral touch, etc.) and non-oral part (non oral-thermosensation, pain, etc.) which are anatomically and functionally highly similar. Consistent with this new concept and with a large volume of experimental data, I propose that awareness of intraoral food is related to the concomitant reverberant self-sustained activation of a coalition of neuronal subsets in agranular insula and orbitofrontal cortex (affect, hedonics) and agranular insula and perirhinal cortex (food identity), as well as the amygdala (affect and identity) in humans. I further discuss the functional anatomy in relation essential nodes. These formulations are by necessity to some extent speculative.

Brain↗
PubMed1995

Verapamil and flunarizine protect the isolated perfused rat liver against warm ischemia and reperfusion injury.

Using the model of the isolated perfused rat liver, we investigated the influence of the two pharmacologically different calcium channel blockers, verapamil and flunarizine, on changes of ion homeostasis, liver weights, pH deviations and enzyme activities during warm ischemia (37 degrees C) and reperfusion. The LDH and GLDH activities were determined and the calcium, potassium, and sodium concentrations were measured in the effluent. Warm ischemia (180 min) caused an increased enzyme release, a high influx of calcium and sodium into the liver and a massive potassium efflux current. Normoxic reperfusion led to a further increase in hepatic enzyme release and although the loss of potassium ceased, the calcium influx into the liver continued. By the end of reperfusion the liver weight had increased significantly (P < 0.01) in the control group. The two calcium entry blockers were added to the perfusate in various concentrations. Both substances protected the liver against warm ischemia and normoxic reperfusion damage, but they did not inhibit calcium inflow. However, the potassium efflux was significantly reduced by all concentration tasted (P < 0.001). After reperfusion the liver weights were significantly lower in the treated groups (P < 0.001) than in control animals. Thus, the calcium entry blockers verapamil and flunarizine protect liver cells against damage caused by warm ischemia and reperfusion. Furthermore, they prevent the disruption of intracellular potassium homeostasis, which seems to be related to improved volume regulation of liver cells.

Animals↗
PubMed1999

Altering the fat content affects flavor release in a model yogurt system.

Flavored yogurts differing in fat content were eaten, and the release of flavor volatiles was measured by monitoring the volatile composition of air from the nose in real time by atmospheric pressure ionization mass spectrometry. Low-fat yogurts (0.2%) were found to release volatiles more quickly and at higher intensity but with less persistence than yogurts containing fat at 3.5 and 10% fat. Yogurts with increasing fat content had higher viscosity and lower relative particle size. Lipophilic compounds were more affected by fat for maximum volatile intensity, but not time-to-maximum intensity or persistence. Sensory assessment of the yogurts found significant differences in intensity and speed of onset of flavor, but not overall length of perception.

Animals↗
PubMed2000

Silver acetate for smoking cessation.

BACKGROUND: Silver acetate produces an unpleasant taste when combined with cigarettes, thereby producing an aversive stimulus. It has been marketed in various forms with the aim of extinguishing the urge to smoke, by pairing the urge with an unpleasant stimulus. OBJECTIVES: The aim of this review was to determine the effectiveness of silver acetate products (gum, lozenge, spray) in promoting smoking cessation. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register. SELECTION CRITERIA: We included randomised trials of silver acetate for smoking cessation with reports of smoking status at least six months after the beginning of treatment. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects, the dose and form of silver acetate, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was biochemically validated abstinence from smoking after at least six months follow-up in patients smoking at baseline. Subjects lost to follow-up were counted as continuing smokers. Where appropriate, we performed meta-analysis using a fixed effects model. MAIN RESULTS: Two studies provided long-term follow-up data on patients randomised to silver acetate or placebo. In one of these studies, there was a third arm, randomised to 2mg nicotine gum. The combined odds ratio for quitting for silver acetate vs placebo was 1.05 (95% confidence interval 0.63 to 1.73). REVIEWER'S CONCLUSIONS: Existing trials show little evidence for a specific effect of silver acetate in promoting smoking cessation. The confidence intervals for the ratio are quite wide. However, the upper limit of the confidence intervals for a positive effect equates to an absolute increase in the smoking cessation rate of about 4%. Any effect of this agent is therefore likely to be smaller than nicotine replacement therapy. The lack of effect of silver acetate may reflect poor compliance with a treatment whose rationale is to create an unpleasant stimulus.

Acetates↗
PubMed2004

The C. elegans thermosensory neuron AFD responds to warming.

The mechanism of temperature sensation is far less understood than the sensory response to other environmental stimuli such as light, odor, and taste. Thermotaxis behavior in C. elegans requires the ability to discriminate temperature differences as small as approximately 0.05 degrees C and to memorize the previously cultivated temperature. The AFD neuron is the only major thermosensory neuron required for the thermotaxis behavior. Genetic analyses have revealed several signal transduction molecules that are required for the sensation and/or memory of temperature information in the AFD neuron, but its physiological properties, such as its ability to sense absolute temperature or temperature change, have been unclear. We show here that the AFD neuron responds to warming. Calcium concentration in the cell body of AFD neuron is increased transiently in response to warming, but not to absolute temperature or to cooling. The transient response requires the activity of the TAX-4 cGMP-gated cation channel, which plays an essential role in the function of the AFD neuron. Interestingly, the AFD neuron further responds to step-like warming above a threshold that is set by temperature memory. We suggest that C. elegans provides an ideal model to genetically and physiologically reveal the molecular mechanism for sensation and memory of temperature information.

Animals↗
PubMed2003

Contribution of benzenemethanethiol to smoky aroma of certain Vitis vinifera L. wines.

Benzenemethanethiol, a volatile thiol with a strong empyreumatic aroma reminiscent of smoke, has been identified in boxwood (Buxus sempervirens L.) as well as in red and white Vitis vinifera L. wines. The perception threshold in a model hydroalcoholic solution is approximately 0.3 ng/L. All of the wines analyzed for this study contained this compound in concentrations of several dozen nanograms per liter. The Chardonnay wines had 30-40 ng/L. Sensory discrimination between a wine containing 7 ng/L benzenemethanethiol and the same wine with an additional 4 ng/L is very significant; the difference in smell is described as "empyreumatic". This compound can therefore significantly contribute to the aroma of certain wines (Sauvignon Blanc, Semillon, Chardonnay, etc.) containing concentrations as high as 30-100 times higher than their perception threshold.

Benzaldehydes↗
PubMed1997

The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel.

BACKGROUND: Versutoxin (delta-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. delta-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; delta-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of delta-ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. RESULTS: The solution structure of delta-ACTX-Hv1, determined using NMR spectroscopy, comprises a core beta region containing a triple-stranded antiparallel beta sheet, a thumb-like extension protruding from the beta region and a C-terminal 310 helix that is appended to the beta domain by virtue of a disulphide bond. The beta region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with mu-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, delta-ACTX-Hv1 shows both sequence and structural homology with gurmarin, a plant polypeptide. This similarity leads us to suggest that the sweet-taste suppression elicited by gurmarin may result from an interaction with one of the downstream ion channels involved in sweet-taste transduction. CONCLUSIONS: delta-ACTX-Hv1 shows no structural homology with either sea anemone or alpha-scorpion toxins, both of which also modify the inactivation kinetics of voltage-gated sodium channels by interacting with channel recognition site 3. However, we have shown that delta-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and alpha-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.

Agatoxins↗
PubMed2006

Gene expression and specificity in the mature zone of the lobster olfactory organ.

The lobster olfactory organ is an important model for investigating many aspects of the olfactory system. To facilitate study of the molecular basis of olfaction in lobsters, we made a subtracted cDNA library from the mature zone of the olfactory organ of Homarus americanus, the American lobster. Sequencing of the 5'-end of 5,184 cDNA clones produced 2,389 distinct high-quality sequences consisting of 1,944 singlets and 445 contigs. Matches to known sequences corresponded with the types of cells present in the olfactory organ, including specific markers of olfactory sensory neurons, auxiliary cells, secretory cells of the aesthetasc tegumental gland, and epithelial cells. The wealth of neuronal mRNAs represented among the sequences reflected the preponderance of neurons in the tissue. The sequences identified candidate genes responsible for known functions and suggested new functions not previously recognized in the olfactory organ. A cDNA microarray was designed and tested by assessing mRNA abundance differences between two of the lobster's major chemosensory structures: the mature zone of the olfactory organ and the dactyl of the walking legs, a taste organ. The 115 differences detected again emphasized the abundance of neurons in the olfactory organ, especially a cluster of mRNAs encoding cytoskeletal-associated proteins and cell adhesion molecules such as 14-3-3zeta, actins, tubulins, trophinin, Fax, Yel077cp, suppressor of profilin 2, and gelsolin.

Animals↗
PubMed2001

Verification of a mouth simulator by in vivo measurements.

The volatile content of the effluent from the retronasal aroma simulator (RAS) was compared with that of human breath using mass spectroscopy (MS-Nose). The ratios of volatile compounds from the RAS were closely related to those from the panelists' breath with the correlation coefficients ranging from 0.97 to 0.99 from model food systems. A greater sensitivity using the RAS was achieved because higher concentrations of volatiles in the MS-Nose were produced from the RAS than from the breath. In analyzing the effects on volatility of RAS parameters including airflow rate, temperature, saliva ratio, and blending speed, airflow rate had the greatest effect. The correlation coefficients for the real food systems studied ranged from 0.83 to 0.99. The RAS gives a good approximation of time-averaged flavor release in the mouth as defined by breath-by-breath measurements.

Adult↗
PubMed2007

Quantitative structure-activity relationship study of bitter di- and tri-peptides including relationship with angiotensin I-converting enzyme inhibitory activity.

Bitterness represents a major challenge in industrial application of food protein hydrolysates or bioactive peptides and is a major factor that controls the flavor of formulated therapeutic products. The aim of this work was to apply quantitative structure-activity relationship modeling as a tool to determine the type and position of amino acids that contribute to bitterness of di- and tri-peptides. Datasets of bitter di- and tri-peptides were constructed using values from available literature, followed by modeling using partial least square (PLS) regression based on the three z-scores of 20 coded amino acids. Prediction models were validated using cross-validation and permutation tests. Results showed that a single-component model could explain 52 and 50% of the Y variance (bitterness threshold) of bitter di- and tri-peptides, respectively. Using PLS regression coefficients, it was determined that hydrophobic amino acids at the carboxyl-terminus and bulky amino acid residues adjacent to the carboxyl terminal are the major determinants of the intensity of bitterness of di- and tri-peptides. However, there was no significant (p > 0.05) correlation between bitterness of di- and tri-peptides and their angiotensin I-converting enzyme-inhibitory properties.

Amino Acid Sequence↗
PubMed1993

Purified antichick Thy-1 IgG abolishes intermediate and long-term memory.

One- to 2-day-old chicks administered purified antichick Thy-1 IgG showed substantial amnesia for a single-trial passive discriminated avoidance task. Amnesia was clearly evident at 30 min after learning, during the intermediate stage of a three-stage model of memory processing, and persisted for at least 3 h. A similar effect was also observed with Fab and F(ab')2 fragments. Fc fragments, the non-IgG fraction of ascites, and saline yielded normal retention levels at all times. These results contrast with our earlier reports that both polyclonal and monoclonal antibodies to chick Thy-1 inhibited long-term memory formation only. The present findings are interpreted as possibly representing a dual effect of the purified IgG.

Animals↗
PubMed2001

[The quality of life in head and neck cancer patients: description of randomized examination formula based on standardized questionnaires EORTC QLQ C-30, EORTC QTQ-H-N35 and Kiel Questionnaire].

The notion of quality of life (QL) was first introduced in the US in the 50-ies. This notion is much broader then health, it is a personal, subjective feeling of well-being that comes from actual, widely-meant life experiences. The QL is not a measurable value, however, it may be assessed by means of appropriate indices. In the contemporary holistic attitude to a patient, in modern oncology, QL has become a parameter of equal importance to other values characterizing the treatment success, as important as numbers describing e.g. mean survival, disease free survival, or neoplasm controlled survival. Head and neck neoplasms bring about deterioration of the basic functions of the organism such as: breathing, swallowing, speaking and senses: hearing, taste and smell. Application of treatment may intensify pain, dyspnea, hoarseness or cause any kind of discomfort. It influences directly the patients' family and social life. Comparison of QL of patients treated for larynx, tongue, tonsill, glands, and paranasal sinuses neoplasms depending on localisation of primary foci, advancement of the disease, the applied treatment and its radicality, age, sex, place of living (town/country), and educational level. Correlation between the subjectively assessed QL and the objectively evaluated condition of the patient is measured. In ENT Dept. K. Marcinkowski University of Medical Sciences 46 patients were examined from May to September 2000. EORTC QLQ C-30, EORTC QLQ-Head and Neck and HAD scale were used. Kiel Questionnaire was introduced in September. The main reason for introducing it was the fact, that surgery is the method of choice in the treatment of head and neck malignancies in our Dept. The team composed of a psychologist and an ENT doctor has been working together on objective assessment of each patient. The QL assessment may be of practical importance when trying to improve the model of health care in cases of oncological patients. This knowledge enables us to learn how the accompanying side effects of therapy influence the QL of our patients, and how these problems may be overcome by proper education, advice, and support provided by the qualified staff. The authors are evaluating the QL in the period of 2, 6 months and 1 year after surgery in patients not supported psychologically. Our goal, in the future, is to introduce the psychological treatment, i.e. repetitive meetings in small groups, conducted by a psychologist. We have contacted 4 major ENT centers in Poland in order to coordinate the research on detailed assessment of QL in Head and Neck Cancer Patients in Poland. The results will be presented in the further publications.

Carcinoma, Squamous Cell↗
PubMed2004

Furfuryl ethyl ether: important aging flavor and a new marker for the storage conditions of beer.

Recently, it was reported that furfuryl ethyl ether is an important flavor compound indicative of beer storage and aging conditions. A study of the reaction mechanism indicates that furfuryl ethyl ether is most likely formed by protonation of furfuryl alcohol or furfuryl acetate followed by S(N)2-substitution of the leaving group by the nucleophilic ethanol. For the reaction in beer, a pseudo-first-order reaction kinetics was derived. A close correlation was found between the values predicted by the kinetic model and the actual furfuryl ethyl ether concentration evolution during storage of beer. Furthermore, 10 commercial beers of different types, aged during 4 years in natural conditions, were analyzed, and it was found that the furfuryl ethyl ether flavor threshold was largely exceeded in each type of beer. In these natural aging conditions, lower pH, darker color, and higher alcohol content were factors that enhanced furfuryl ethyl ether formation. On the other hand, sulfite clearly reduced furfuryl ethyl ether formation. All results show that the furfuryl ethyl ether concentration is an excellent time-temperature integrator for beer storage.

Beer↗
PubMed2004

Polyphenolic profiles of Basque cider apple cultivars and their technological properties.

The polyphenolic compositions of 31 Basque cider apple cultivars were determined in pulp, peel, and juice by high-performance liquid chromatography with diode array detection analysis of crude extracts and after thiolysis. Total polyphenols are distributed in a wide concentration range depending on the cultivar. Procyanidins are the class of polyphenols that present major concentrations in apple. Their average degrees of polymerization range from 4 to 8 depending on the cultivar. Apple cultivars were technologically classified into bitter and nonbitter categories using different classification systems obtained by applying several pattern recognition techniques, such as principal component analysis, K-nearest neighbors, soft independent modeling of class analogy, partial least-squares, and multilayer feed-forward-artificial neural networks, to apple pulp, peel, or juice data (individual polyphenol concentrations, total procyanidin content, and the average degree of polymerization of procyanidins). Bitter apple cultivars present higher contents of flavan-3-ols and/or dihydrochalcones than nonbitter cultivars. Detailed knowledge of the polyphenolic profile of each apple cultivar affords information about their susceptibility to oxidation, their sensory properties (bitterness, astringency), and their possible influence on the characteristics and quality of the final product (juice, cider) when apples are processed.

Beverages↗
PubMed2003

[How do G-protein-coupled receptors work? The case of metabotropic glutamate and GABA receptors].

G-protein coupled receptors (GPCRs) represent the largest membrane proteins family in animal genomes. Being the receptors for most hormones and neurotransmitters, these proteins play a central role in intercellular communication. GPCRs can be classified into several groups based on the sequence similarity of their common structural feature: the heptahelical domain. The metabotropic receptors for the main neurotransmitters glutamate and gamma-aminobutyric acid (GABA) belong to the class III of GPCRs, together with others receptors for Ca2+, for sweet and amino acid taste compounds and for some pheromones, as well as for odorants in fish. Besides their transmembrane heptahelical domain responsible for G-protein activation, most of class III receptors possess a large extracellular domain responsible for ligand recognition. The recent resolution of the structure of this binding domain of one of these receptors, the mGlu1 receptor, together with the recent demonstration that these receptors are dimers, revealed an original mechanism of activation for these GPCRs. Such data open new possibilities to develop drugs aimed at modulating these receptors, and raised a number of interesting questions on the activation mechanism of other GPCRs.

Animals↗
PubMed2003

Prevalence and association of welding related systemic and respiratory symptoms in welders.

BACKGROUND: The prevalence of welding related respiratory symptoms coexisting with welding related systemic symptoms in welders is unknown. AIMS: To determine in a sample of welders the prevalence of coexisting welding related systemic symptoms indicative of metal fume fever (MFF) and welding related respiratory symptoms suggestive of occupational asthma (OA), and the strength and significance of any association between these two groups of symptoms. METHODS: A respiratory symptoms questionnaire, a systemic symptoms questionnaire, and a questionnaire on occupational history were administered by telephone to 351 of a sample of 441 welders (79.6%) from two cities in Québec, Canada. RESULTS: The co-occurrence of possible MFF (defined as having at least two symptoms of fever, feelings of flu, general malaise, chills, dry cough, metallic taste, and shortness of breath, occurring at the beginning of the working week, 3-10 hours after exposure to welding fumes) together with welding related respiratory symptoms suggestive of OA (defined as having at least two welding related symptoms of cough, wheezing, and chest tightness) was 5.8%. These two groups of symptoms were significantly associated (chi(2) = 18.9, p < 0.001). CONCLUSION: There is a strong association between welding related MFF and welding related respiratory symptoms suggestive of OA. As such, MFF could be viewed as a pre-marker of welding related OA, a hypothesis that requires further investigation.

Adult↗
PubMed2002

A phase II trial of JM-216 in cervical cancer: an NCIC CTG study.

OBJECTIVE: BMS-182751 (JM-216) is an orally bioavailable platinum compound with activity in platinum-sensitive and platinum-resistant preclinical models. The objective was to determine its activity in recurrent/metastatic squamous cell carcinoma of the cervix. METHODS: We conducted a phase II study of BMS-182751 given at a dose of 30 mg/m(2) daily for 14 days every 5 weeks. RESULTS: Eighteen patients (pts) with advanced/recurrent squamous cancer of the cervix not amenable to curative therapy with measurable disease who had received no prior chemotherapy for systemic disease were entered, all of whom are evaluable for response and toxicity. Median age was 47 years (35-74 years); all pts had received prior pelvic irradiation (RT); 4 pts had received cisplatin as adjustment therapy with radiation; PS was 0 (6 pts), 1 (7 pts), and 2 (5 pts); sites of disease included nodes (10 pts), pelvis (5 pts), lung (4 pts), and bone (3 pts). Median number of cycles was two (1-6) with 8 pts receiving three or more cycles. Toxicity was modest and usually grade 1 or 2 in severity with the most frequent drug related toxicity being nausea (56%), fatigue (50%), anorexia (39%), diarrhea (39%), vomiting (39%), constipation (28%), and altered taste (22%). Six pts had grade 3 or 4 granulocytopenia and only 1 pt, grade 3 or 4 thrombocytopenia. Two pts had grade 2 or 3 creatinine increases. There were no treatment-related deaths. One pt with a treatment-free interval of 30 years achieved a partial response, while 12 pts had a best response of stable disease. CONCLUSIONS: BMS-182751 is generally well tolerated, but has limited activity in pts with recurrent cervical cancer.

Administration, Oral↗