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PubMed2006

[Symptom evaluation as an efficient diagnostic tool for upper abdominal diseases].

INTRODUCTION: GERD and dyspepsia are common conditions, affecting approximately 25-40% of the general population. In the absence of alarm symptoms, the current recommended policy in young dyspeptic patients is a "test and treat" strategy for H. pylori. On the other hand, in GERD patients, a therapeutic trial with proton pump inhibitors (PPI) is the treatment of choice. AIM: This study aimed to create short and simple clinical algorithms, for the diagnosis and treatment of patients with upper gastrointestinal complaints. METHODS: Data mining models and algorithms (neural networks, decision trees and logistic regression) were used to create a diagnostic symptom questionnaire to classify the patients into one of two diagnostic groups: GERD vs. non-GERD. The questionnaire was validated against endoscopic and clinical diagnoses of 132 patients in a cross-sectional study, and was designed to yield a "GERD score". The clinical and economical benefits of the new algorithm were evaluated in primary care clinics in Israel. RESULTS: The symptoms chosen for the diagnostic questionnaire were heartburn, acid regurgitation, sour oral taste, aggravation of symptoms after heavy meals, relief of symptoms by antacids, and nocturnal reflux. The use of the algorithm by primary care physicians improved clinical outcomes and reduced health resources consumption. CONCLUSIONS: This new short algorithm was found to be useful and easy to apply in clinical practice. The questionnaire can be also implemented in computerized medical systems.

Algorithms↗
PubMed1996

Increased liking for salty foods in adolescents exposed during infancy to a chloride-deficient feeding formula.

In a model selected for its similarity to the hormonal consequences of sodium deficiency, food choices of 169 adolescents exposed during infancy to a chloride-deficient feeding formula were compared to those of their closest-aged siblings. Questionnaires completed by parents were used to assess food likes and dislikes. When a salty food was mentioned by parents as one craved by either child, exposed children were more likely than siblings to crave that food (p = 0.005). Frequencies of two of four salt-related dietary behaviors [adding salt to food before tasting (p = 0.03) and to atypical foods (p = 0.05)] were higher in exposed adolescents than in siblings, while frequencies of parallel sugar-related behaviors did not differ between the groups. Foods classified as being lower in saltiness were disliked by exposed children relative to siblings (p = 0.003), although ratings of foods higher in saltiness did not differ. Finally, when asked to rank eight foods in order of preference, ranks assigned by exposed children to salty foods tended (p = 0.07) to be higher than those of siblings. The data suggest a persistent effect of early experience on human salt preference. Additional studies are needed to determine whether salt intake is increased in this and other populations that suffer electrolyte depletion during early development.

Adolescent↗
PubMed1991

Amino acid imbalance, a nutritional model: serotonin3 mediation of aversive responses.

The feeding responses to essential dietary amino acid (AA) disproportion have been useful in nutritional studies. These responses involve first: recognition of the imbalance and second: rejection of the diet, likely via development of a learned aversion. In the rat, we have studied the role of the limiting AA and protein synthesis in the recognition phase by replacement of the limiting AA into a brain area essential for the initial depressed feeding response. We have also reported a reciprocal relationship between serotonin (5HT) activity and intake of imbalanced diets. High doses of the 5HT3 receptor antagonist, ICS 205-930 (ICS; 9 mg/kg IP), restored food intake to 85% or more of control intake. In the present experiments, similar treatment with ICS blocked the classical conditioned taste aversion to a saccharin solution paired with lithium chloride. These results suggest that the increased intake of AA imbalanced diets after ICS may be due to 5HT-mediated blockade of a learned aversion.

Amino Acids↗
PubMed1994

Local and transmitted conformational changes on complexation of an anti-sweetener Fab.

Crystal structures of an Fab (NC6.8) from a murine IgG2b(kappa) antibody and its complex with a sweet-tasting, N-,N'-,N"-trisubstituted guanidine compound (NC174) have been determined by X-ray analysis. Both crystal forms are produced by a microseeding technique in polyethylene glycol (PEG) 8000 but the habits and space groups are very different. The native protein crystallizes as plates in the monoclinic space group C2 and the complex crystallizes as prisms in the orthorhombic space group P2(1)2(1)2. The structures were solved by molecular replacement methods, with the Fab fragments from the 4-4-20, HyHel-5 and BV04-01 antibodies as starting models. On binding of the ligand, N-(p-cyanophenyl)-N'-(diphenylmethyl)-N"-(carboxymethyl)g uan idine, the protein exhibits significant local conformational changes in the active site, particularly in the third complementarity-determining region (CDR3) of the heavy chain. The ligand enters the small crevice by end-on insertion with the cyanophenyl group in the lead and the diphenyl rings partially protruding from the entrance. No strict pi-pi stacking interactions are observed. However, tyrosine L32 (CDR1), tyrosine L96 (CDR3) and tryptophan H33 (CDR1) help immobilize the cyanophenyl ring and guanido group, and tyrosine H96 moves about 4.5 A to lie between the rings of the diphenyl group. The positive charge on the guanido group is compensated by glutamic acid H50 (CDR2) while the negative charge on acetic acid is neutralized by arginine H56 (CDR2) and by hydrogen bonding with asparagine H58 (CDR2). Water molecules participate in the binding process by hydrogen bonding with the cyano and guanido groups. The mechanism of binding is a clear example of induced fit. Like hemoglobin, the NC6.8 Fab can be classified as an allosteric protein, since its overall structure is altered by the binding of a small ligand. In crystals of the native Fab the elbow bend angle is 184 degrees while in crystals of the complex the elbow angle is 153 degrees. There is also a reciprocal push-pull type of change where the heavy chain is flexed and the light chain is extended. The tail of the heavy chain, which would be connected to the Fc in an intact antibody, is displaced 19 A relative to its position in the unliganded Fab. Within the limited series of sweetener-Fab complexes we have thus far examined, only the NC174 hapten has produced such results.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗
PubMed1993

Analysis of sensory and physicochemical data on commercial tomato purée with pattern recognition techniques.

The correlations between analytical parameters and some typical sensory attributes of commercial tomato purée (8-14 degrees Brix) were studied. In order to ensure the widest possible variance multivariate analyses was used. A model was obtained that could describe the different contribution of the analytical variables to the sensory attributes examined. Cluster analysis revealed the existence of two distinct sub-groups; traditional by tomato purée and organically produced tomato purée.

Acetoin↗
PubMed2006

Modelling of sensory and instrumental texture parameters in processed cheese by near infrared reflectance spectroscopy.

This study investigated the application of near infrared (NIR) reflectance spectroscopy to the measurement of texture (sensory and instrumental) in experimental processed cheese samples. Spectra (750 to 2498 nm) of cheeses were recorded after 2 and 4 weeks storage at 4 degrees C. Trained assessors evaluated 9 sensory properties, a texture profile analyser (TPA) was used to record 5 instrumental parameters and cheese 'meltability' was measured by computer vision. Predictive models for sensory and instrumental texture parameters were developed using partial least squares regression on raw or pre-treated spectral data. Sensory attributes and instrumental texture measurements were modelled with sufficient accuracy to recommend the use of NIR reflectance spectroscopy for routine quality assessment of processed cheese.

Adult↗
PubMed1988

Corrosion current and pH rise around titanium coupled to dental alloys.

Corrosion reactions around titanium, usually considered biologically inert, might be provoked by coupling it galvanically with more corrodible dental alloys. Experiments in vitro simulating the conditions of a titanium dental implant or root canal post coupled to an amalgam filling, demonstrated corrosion current densities up to 31 microA/cm2, anodic pH values around the amalgam down to 2, and cathodic pH values around the titanium up to 10. The amounts of tin released by the enhanced corrosion of amalgam might contribute measurably to the daily intake of this element; the corrosion current generated reached values known to cause taste sensations. If the buffer systems of adjacent tissues in vivo are not able to cope with the high pH generated around the titanium, local tissue damage may ensue; this relationship is liable to be overlooked, as it leaves no evidence in the form of corrosion products.

Corrosion↗
PubMed2003

Chemosensory tuning to a host recognition cue in the facultative specialist larvae of the moth Manduca sexta.

Larvae of Manduca sexta are facultative specialists on plants in the family Solanaceae. Larvae reared on solanaceous foliage develop a strong preference for their host; otherwise, they remain polyphagous. The host-specific recognition cue in potato foliage for Manduca larvae is the steroidal glycoside, indioside D. Two pairs of galeal taste sensilla, the lateral and medial sensilla styloconica, are both necessary and sufficient for the feeding preferences of host-restricted larvae. We conducted electrophysiological tip recordings from sensilla of solanaceous or wheat germ diet-reared larvae. For each animal, recordings of the responses to indioside D, glucose, tomatine and KCl were compared. All responses included both phasic and tonic portions. The sensilla styloconica of solanaceous-reared larvae were tuned to indioside D, defined as maintaining a high sensitivity to indioside D, while showing lower sensitivity to other plant compounds. Half of the sensillar neurons of solanaceous-reared larvae were 'tuned' to indioside D, whereas those of wheat germ diet-reared larvae were not. The different responses between the two types of animals were a result of changes of individual receptor cells' responses in the sensilla. Feeding on solanaceous foliage therefore appears to result in a modification of the physiological responses of individual taste receptor cells that causes them to be tuned to the host-recognition cue indioside D. We propose that this tuning is the basis for the host-restricted larvae's strong behavioral preferences for solanaceous foliage.

Analysis of Variance↗
PubMed1991

An ethopharmacological approach to the development of drug addiction.

In a rat model of alcoholism, different stages of the development towards a drug addiction can be discriminated. During the phase of "controlled" intake, drug consumption is reversibly modified by the social situation (housing conditions) and the individual's social role (in particular his dominance rank). In Wistar rats, this period lasts about half a year. During the next few months, the consumption of ethanol rises without a concomitant loss of its behavioral effects. After an abstinence period of nine months, the rats maintain a high preference for alcohol which cannot be suppressed by adulteration with (unpleasantly tasting) quinine. Ethanol-taking behavior can no longer be modified by external stimuli or by dominance rank. This irreversible state is called "behavioral dependence." It is drug-specific (i.e., other drugs like diazepam cannot substitute the alcohol) and not related to physical dependence. In behaviorally dependent rats, the effects of ethanol are altered; very low doses tranquillize the rats, higher ones stimulate them.

Animals↗
PubMed1993

Gadodiamide injection. First human experience with the nonionic magnetic resonance imaging enhancement agent.

The safety, tolerance, and pharmacokinetics of gadodiamide injection (Omniscan, Sanofi Winthrop Pharmaceuticals, New York, NY) were evaluated in an open, ascending-dose study in 20 healthy male volunteers. Gadodiamide injection was administered intravenously at doses of 0.05, 0.1, 0.2, and 0.3 mmol/kg. Mild adverse events were experienced by nine subjects. These events included, but were not limited to, light-headedness, dizziness, and perversion of taste or smell. There was one occurrence of injection-associated discomfort that resolved within seconds. Vital sign and electrocardiogram measurements did not show any clinically relevant changes. There were no clinically significant changes in laboratory parameters, but minor transient elevations in serum iron were detected. These elevations typically occurred 8 and 48 hours after administration of gadodiamide injection and were not dose related. The pharmacokinetics of gadodiamide injection were evaluated in the 0.1-mmol/kg and 0.3-mmol/kg dose groups with the serum time-concentration data fitted to an open two-compartment model and the urine time-concentration data fitted to a one-compartment model. The serum elimination half-life was approximately 70 minutes, and urinary recovery was greater than 95% by 72 hours after administration.

Adult↗
PubMed1989

The marriage premium and compensating wage differentials.

This paper proposes and tests an alternative explanation of the marriage premium that relies upon differences in workers' tastes and compensating wage differentials. A key assumption is that marital status proxies for the consumption of family goods, such as children, and that these are costly. Workers whose greater demands for family goods are taste- generated and shown to choose jobs that offer greater wage, and less non-pecuniary compensation. This creates an observed wage premium that has nothing to do with differences in workers' productivities. Supporting empirical evidence for this hypothesis is presented, including a reevaluation of previous studies.

Americas↗
PubMed2003

Potential of gas chromatography-orthogonal acceleration time-of-flight mass spectrometry (GC-oaTOFMS) in flavor research.

Gas chromatography-orthogonal acceleration time-of-flight mass spectrometry (GC-oaTOFMS) is an emerging technique offering a straightforward access to a resolving power up to 7000. This paper deals with the use of GC-oaTOFMS to identify the flavor components of a complex seafood flavor extract and to quantify furanones formed in model Maillard reactions. A seafood extract was selected as a representative example for complex food flavors and was previously analyzed using GC-quadrupole MS, leaving several molecules unidentified. GC-oaTOFMS analysis was focused on these unknowns to evaluate its potential in flavor research, particularly for determining exact masses. N-Methyldithiodimethylamine, 6-methyl-5-hepten-2-one, and tetrahydro-2,4-dimethyl-4H-pyrrolo[2,1-d]-1,3,5-dithiazine were successfully identified on the basis of the precise mass determination of their molecular ions and their major fragments. A second set of experiments was performed to test the capabilities of the GC-oaTOFMS for quantification. Calibration curves were found to be linear over a dynamic range of 10(3) for the quantification of furanones. The quantitative data obtained using GC-oaTOFMS confirmed earlier results that the formation of 4-hydroxy-2,5-dimethyl-3(2H)-furanone was favored in the xylose/glycine model reaction and 2(or 5)-ethyl-4-hydroxy-5(or 2)-methyl-3(2H)-furanone in the xylose/alanine model reaction. It was concluded that GC-oaTOFMS may become a powerful analytical tool for the flavor chemist for both identification and quantification purposes, the latter in particular when combined with stable isotope dilution assay.

Animals↗
PubMedDate not supplied

[Ion channels that are sensitive to the extracellular concentration of protons: their structure, function, pharmacology and pathophysiology].

AIM: Acid sensing ion channels (ASIC) members of the ENaC degenerine channel family, have been shown to participate in various sensorial pathways including nociception, also they have been shown to participate in synaptic transmission, learning and memory processes and in the physiopathology of the ischemic stroke. DEVELOPMENT: The proton concentration in the organism is strictly regulated by distinct buffer systems. Drastic changes of pH are generated only by pathological conditions as is the ischemia; however, some physiological processes may produce local changes in the extracellular pH. Recently, a new family of proton receptors known as ASIC has been cloned. These are ionic channels inactivated at physiological pH (7.4) and activated with a pH fall (increase in H+ concentration). ASICs are permeable to sodium ions and in a lesser degree to calcium ions, activation of these channels leads to an increase in cell excitability. The ASICs are distributed widely in the central and peripheral nervous system, and in specialized epithelia. In the past few years they have become a focus of interest due to its role in nociception, taste perception, long term potentation and the physiopathology of ischemic stroke. CONCLUSIONS: In this review we address the most relevant molecular, physiological and pharmacological aspects of the ASICs, its participation in some pathological process, and the perspectives of basic and clinic investigation in this arising research field.

Acid Sensing Ion Channels↗
PubMed1993

Feeding behavior of grazing ruminants experiencing stress.

The mechanisms underlying diet selection of ruminants are less studied than those for monogastrics. However, recent studies have shown that these mechanisms may be more similar in ruminants and monogastrics than previously believed. Food aversion learning is observed in both monogastrics and ruminants, and the hypothalamic-pituitary-adrenal axis appears to be involved in avoidance learning. Using leafy spurge (Euphorbia esula), an introduced weed whose expansion has costly ecological and economic implications in western North America, as a model for underconsumed plant species, we hypothesized that sheep experience increased cortisol levels when they first consume leafy spurge and that this may be related to their reluctance to graze it. We also hypothesized that preexposure to leafy spurge would attenuate the development of a spurge-based aversion. Correspondingly, we hypothesized that preexposed sheep would not experience increased blood cortisol levels with leafy spurge gavage during an aversion trial. None of our hypotheses were disproved by the experiments. Our results lend support to the hypothesis that stress is required for the development of conditioned taste aversions and extend it to ruminants. We suggest that activity of the hypothalamic-pituitary-adrenal axis is integral to food aversion learning in ruminants.

Animals↗
PubMed1995

Phase I and clinical evaluation of a pharmacologically guided regimen of suramin in patients with hormone-refractory prostate cancer.

PURPOSE: This phase I study was designed with the following objectives: (1) to describe the overall and dose-limiting toxicity (DLT) of suramin administered by intermittent short intravenous infusions until DLT or disease progression; (2) to determine the ability of an adaptive control with feedback (ACF) dosing strategy to maintain suramin plasma concentrations within a preselected range; (3) to develop a population model of suramin pharmacokinetics; and (4) to identify preliminary evidence of antitumor activity. PATIENTS AND METHODS: Seventy-three patients with advanced, incurable, solid tumors (including 69 with hormone-refractory prostate cancer) received an initial 5- to 7-day daily loading treatment followed by intermittent infusions individually determined by ACF using a Bayesian algorithm and relying on population models of suramin pharmacokinetics. Treatment was given to three cohorts of patients based on target plasma suramin concentration ranges (peak, 30 minutes postsuramin, and trough on morning of the treatment day), as follows: cohort 1, 175 to 300 micrograms/mL (27 patients); cohort 2, 150 to 250 micrograms/mL (23 patients); and cohort 3, 100 to 200 micrograms/mL (23 patients). All patients were to receive suramin until DLT or disease progression. RESULTS: The DLT was most commonly seen in cohort 1 and included a syndrome of malaise and fatigue, associated with weight loss, anorexia, and changes in taste. Other reversible toxicities were neurologic, renal, cutaneous, edema, lymphopenia and anemia, ophthalmologic, and alopecia. Forty of 67 assessable patients (60%) had a 50% reduction and 25 of 67 (37%) a 75% reduction in prostate-specific antigen (PSA) levels that lasted more than 4 weeks, seven of 18 (40%) had measurable responses, and 18 of 37 (49%) demonstrated major pain improvement. The overall times to disease progression and survival were 170 and 492 days, respectively. CONCLUSION: We have characterized all toxicities with suramin in a pharmacologically guided phase I study designed to maintain plasma suramin concentrations of 100 to 300 micrograms/mL (cohorts 1 to 3). The incidence of grade 3 to 4 neurologic abnormalities was relatively low, particularly in cohorts 2 and 3 (100 to 250 micrograms/mL). Evidence of significant and durable antitumor activity was seen in all three cohorts.

Adaptation, Physiological↗
PubMed1979

Biting activity by Aedes egypti mosquitoes in guinea-pigs. An experimental model for screening the effect of some systemically administered compounds.

The Aedes egypti mosquito fed consistently on guinea-pigs in a 2-hour period (n = 61), the mean percent feeding rate (+/- S.D.) being 88.84 +/- 9.32. Of a total of 34 different compounds systematally administered in guinea-pigs and tested for their effect on the mosquito biting rate using the above model, five: heparin, sodium fluoride, aminocaproic acid, thiourea and dithiocarb partially reduced the biting rate. The results are consistent with the view that certain aminoacids or proteins of blood or tissues serve as 'pheromones' attracting the mosquito to guinea-pigs.

Aedes↗
PubMed1998

Phase I clinical trial of perillyl alcohol administered daily.

Perillyl alcohol (POH; NSC-641066), a naturally occurring monoterpene, has shown antitumor and preventive activity in preclinical studies in rodent models. Drug-related activities that have been observed include the induction of apoptosis, cell cycle arrest, the inhibition of posttranslational modification of proteins that are involved in signal transduction, and differential gene regulation. We treated 18 patients who had advanced malignancies with POH, which was given on a continuous three-times-a-day schedule at the following doses: (a) level 1 (L1), 800 mg/m2/dose; (b) level 2 (L2), 1600 mg/m2/dose; and (c) level 3 (L3), 2400 mg/m2/dose. The main toxicity, which seemed to be dose related, was gastrointestinal and included nausea and vomiting, anorexia, unpleasant taste, satiety, and eructation. Two heavily pretreated ovarian cancer patients experienced reversible > or =grade 3 granulocytopenia. Grade 1-2 fatigue was also noted. The parent drug was not detectable in the plasma. The mean peak plasma levels of the two main metabolites on days 1 and 29 were 175 and 139 microM (L1), 472 and 311 microM (L2), and 456 and 257 microM (L3) for perillic acid (PA) and 7.1 and 9.8 microM (L1), 34.2 and 34.0 microM (L2), and 26.2 and 23.4 microM (L3) for dihydroperillic acid (DHPA). Peak levels were noted 2-3 h postingestion for PA and 3-5 h postingestion for DHPA. Metabolite half-lives measured about 2 h for each. POH, PA, and DHPA were detectable in the urine of all patients at L3. About 9% of the total dose was recovered in the first 24 h. The majority was recovered as PA; less than 1% was recovered as POH. Disease stabilization for > or =6 months was seen, although no objective tumor responses were noted. Further study of POH continues with a more frequent dosing schedule.

Adult↗
PubMed2000

Flavour conditioning and alcohol: a multilevel model of individual differences.

Previous research shows that dependent drinkers respond more strongly to alcohol-related cues and suggests that alcohol cue-reactivity may be relevant to understanding dependence liability. However, a significant weakness in many studies is the fact that cue-reactivity is studied without actually conditioning subjects; responses to alcohol-related cues are simply assumed to be conditioned responses. The current report attempts to overcome this weakness by studying alcohol cue-reactivity following a flavour-conditioning procedure. A statistical model of individual differences in cue-reactivity was constructed using previous alcohol exposure, alcohol tolerance, and personality as predictor variables. Although there was no evidence for overall differences in subjective and psychophysiological responses to alcohol and soft-drink paired flavours, there were marked individual differences in responding to the different flavours. The statistical model showed that reward sensitivity (high extroversion, high neuroticism), heavier levels of drinking, and higher levels of tolerance to the intoxicating effects of alcohol were associated with lower levels of skin conductance in the presence of alcohol paired flavours.

Adult↗