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Biomedical subjects

F Lucas

Publications and source records attributed to F Lucas.

At least 37 records · Page 2Linked to original sources

Carbohydrate-conditioned odor preferences in rats.

The effectiveness of odor cues to support nutrient-conditioned flavor preferences in rats was studied. When the rats drank fluid, the CS+ odor was paired with intragastric (IG) infusions of Polycose, and the CS- odor with IG water. In Experiment 1, rats trained with almond and anise odors presented with plain drinking water failed to acquire a CS+ odor preference. In contrast, rats in Experiment 2 formed a strong aversion to anise (or almond) paired with lithium chloride, which indicated that the odors were distinguishable to the rats. Experiment 3 showed that providing unique tastes (bitter or sour) in combination with the odors during training potentiated odor conditioning. The rats displayed a strong preference for the odor+taste CS+ and for the odor component alone. Experiment 4 showed that with another pair of odor (peppermint and vanilla), CS+ preferences could be conditioned in the absence of taste cues during training. These results demonstrate that rats can acquire strong nutrient-conditioned odor preferences.

Animals↗

A novel model of a metastatic human breast tumour xenograft line.

The GI-101 human breast tumour xenograft line is unique in that it spontaneously metastasizes to the lungs of athymic murine hosts from subcutaneous trochar implants. Both tumour and lung metastases are positive for normal human breast tissue markers. GI-101 also is positive for the p53 antigen but negative for the c-erbB-2 oncogene.

Animals↗

Effect of oral Saccharomyces boulardii treatment on the activity of Clostridium difficile toxins in mouse digestive tract.

Human antibiotic-associated diarrhoea and pseudomembranous colitis are partly due to toxin production by Clostridium difficile. It is now well documented that Saccharomyces boulardii protects against C. difficile induced diseases. In an attempt to understand better the mechanism of this protective effect, the action of S. boulardii on a crude toxin preparation was studied in vitro and in vivo. The results showed that the yeast had no effect on the toxins in vitro but was able to protect mice inoculated with these toxins. Furthermore, the observation by scanning electron microscopy that the mucosa of S. boulardii protected mice was not damaged suggest that the yeast mainly acts on the intestinal mucosa.

Administration, Oral↗

Sleep polygraphic variables in anorexia nervosa and depression: a comparative study in adolescents.

Sleep EEG variables were compared in an adolescent population consisting of 11 anorectic girls, 11 young depressed patients and 11 healthy volunteers matched for age and sex. Anorectic patients differed from depressed patients in a greater number and a higher length of awakenings. In comparison with controls, anorectic patients showed less sleep efficiency, a higher length of awakenings and less REM sleep. When anorectic patients were divided in restricting and bulimic subtypes, the bulimic anorectics showed an increase in stage 3 of sleep. These results do not support a direct association between eating disorders and affective disorders. Sleep EEG variables were not significantly correlated to the Body Mass Index.

Adolescent↗

Twenty-four-hour patterns of sleep in depression.

Alterations of nocturnal sleep have been widely described in affective disorders. However, little is known about putative daytime sleep and to what extent daytime sleep could interfere with nocturnal sleep. The goal of this study was to investigate 24-hr sleep patterns in 12 depressed patients hospitalized for a major depressive disorder and in 10 control subjects studied under the same experimental conditions. Patients and controls were free to sleep whenever they chose, and sleep recordings were performed using the Oxford Medilog System during 60 hr. Daytime sleep episodes were detected in 50% of the patients and in 60% of the controls. Patients took naps at various times of the day, whereas controls napped in the early afternoon, during the well-known "postlunch dip". Thus daytime sleep prevalence was similar in both groups; however, the biphasic distribution of sleep observed in controls disappeared in the patients. Napping did not affect subsequent nocturnal sleep in either group.

Adult↗

[The receptors for bacterial enterotoxins].

Bacterial enterotoxins, produced by some pathogenic bacteria, induce diarrhoea during human or animal digestive infections; most of them act via membrane receptors and are specifically recognized on the enterocyte brush border. These receptors differ in number (which probably determines the degree of enterotoxin toxicity, nature, structure, and specificity. The receptors, ie glycolipids (GM1) or glycoproteins, are well represented on the surface of the enterocyte, and/or in various vertebrate cell types. The enterotoxins bind to the receptor glucoside chains, in which sequences have sometimes been determined. In most cases irreversible binding occurs due to enterotoxin internalization.

Animals↗

[Bacterial enterotoxins: structure, mode of action].

The enterotoxins are macro-proteins, produced by enterotoxic bacterial strains acting in the human or animal intestine during digestive infections. In most cases, they induce diarrhoea (associated or not with tissue damage). These molecules differ in their structure and mechanism of action. Some of them (cholera toxin, Escherichia coli LT) activate a cyclase system (adenylate or guanylate cyclase), inducing water and electrolyte flux in the gut. Conversely, others (toxins A and B, Clostridium difficile; Clostridium perfringens enterotoxin; verotoxin), provoke diarrhoea, intestinal damage associated with inflammatory response acting on cellular functions (protein synthesis, permeability to small molecules). Most enterotoxins act via membrane receptors which they specifically recognize on the surface of the enterocyte.

Animals↗

Hyperphagia in rats produced by a mixture of fat and sugar.

The hyperphagic and weight-promoting effects of feeding rats a sugar-fat mixture were compared to those of presenting only one of the two nutrients. Experimental groups were fed sugar (sucrose), fat (corn oil), or a sugar-fat mixture as an option to chow; options were in the form of water solutions or emulsions. The control group was fed only chow. The sugar-fat group displayed a robust hyperphagia (greater than 36%), relative to the control group; the hyperphagic response was greater than that observed in the fat group but not in the sugar group. The sugar-fat group selected more calories from the option than the other two experimental groups. Body weight gains were also greater in the sugar-fat group than in the fat and sugar groups. Addition of saccharin to the fat emulsion increased fat and total intakes to levels close to those of the sugar-fat mixture. In a second experiment, the relative palatability of the plain and sweet fat emulsions was assessed with two-bottle preference tests. The sugar-fat mixture was preferred to the saccharin-fat mixture, which in turn was preferred to the plain-fat emulsion. These results suggest that the sweetness of the sugar-fat mixture contributed to the pronounced hyperphagia and obesity obtained with this diet option.

Animals↗

Prevention of Clostridium difficile-induced experimental pseudomembranous colitis by Saccharomyces boulardii: a scanning electron microscopic and microbiological study.

The ability of Saccharomyces boulardii to protect mice against intestinal pathology caused by toxinogenic Clostridium difficile was studied. Different regions of the intestine of experimental mice were prepared for observation by scanning electron microscopy or homogenized for C. difficile enumeration and quantification of toxin A by enzyme immunoassay and toxin B by cytotoxicity. The test group was treated for 6 d with an S. boulardii suspension in drinking water and challenged with C. difficule on day 4. The three control groups were: axenic mice, mice treated with only S. boulardii and mice only challenged with C. difficile. The results showed that: (i) 70% of the mice infected by C. difficile survived when treated with S. boulardii; (ii) the C. difficile-induced lesions on the small and large intestinal mucosa were absent or markedly less severe in S. boulardii-treated mice; and (iii) there was no decrease in the number of C. difficile but rather a reduction in the amount of toxins A and B in S. boulardii-treated mice.

Animals↗

Flavor preferences conditioned by intragastric fat infusions in rats.

The present series of experiments determined if rats would learn to prefer cue flavors that were paired with intragastric (IG) infusions of fat. Adult female rats were fitted with gastric catheters and were trained to drink a flavored (CS+) solution, e.g., cherry-water, associated with IG infusions of a corn oil emulsion. On other days, an alternately flavored (CS-) solution, e.g., grape-water, was paired with IG infusions of water. The preference between the CS solutions was then assessed with 2-bottle choice tests. In Experiment 1, food-restricted rats were given saccharin-sweetened CS solutions for 10 min/day followed by IG infusions of a 7.1% oil emulsion or water. In subsequent choice tests they displayed a small (60%) but significant preference for the CS+ solution. In Experiments 2-5, rats had access to the CS solutions for 20 or 23 hr/day; drinking the CS solutions automatically triggered IG infusions of oil or water (electronic esophagus preparation). Infusions of 7.1% oil failed to produce a significant preference for the CS+ solution in rats given ad lib access to chow, and offered unsweetened CS flavors. Increasing the oil concentration (14.5% and 29%) did not facilitate the formation of a preference, nor did infusing the rats with a preingested oil emulsion. However, rats restricted to 2 hr/day access to chow, and 20 hr/day access to the CS solutions acquired a significant (85%) preference for the CS+ flavor; subsequent training and testing with saccharin-sweetened CS solutions increased the preference for the CS+ flavor to 95%. Ad lib fed rats trained with saccharin-sweetened CS solutions also developed a reliable preference (76%) for the CS+ flavor paired with IG oil; this preference persisted during four extinction tests when both CS+ and CS- flavors were paired with IG water. These results demonstrate that, as with other macronutrients (carbohydrate, protein), the postingestive effects of fats can condition flavor preferences, and suggest that the postingestive actions of nutrients play an important role in food selection and reward.

Animals↗

Dietary fat-induced hyperphagia in rats as a function of fat type and physical form.

The influence of dietary fat on food intake and weight gain was assessed by feeding adult female rats diets that differed in the type and form of fat, as well as in the availability of other macro- and micronutrients. Compared to chow-fed controls, the various fat diets increased total food intake by 4% to 27%. Specifically, rats fed chow and a separate source of fat (fat option diet) consumed more fat and total calories, and gained more weight when the fat source was emulsified corn oil rather than pure corn oil or was vegetable shortening rather than corn oil. However, corn oil and shortening had similar effects on caloric intake and weight gain when presented as emulsified gels. Also, pure and emulsified-gel forms of shortening did not differ in their effects on caloric intake and weight gain. Supplementing the vegetable shortening with micronutrients, however, enhanced its hyperphagia-promoting effect. The results of two-choice tests revealed that the rats' preferences for the orosensory properties of the various fat sources did not account for the differential hyperphagias obtained. Rather, it appears that long-term fat selection and caloric intake are influenced primarily by postingestive factors. Fat selection and total intake were determined not only by the fat source itself, but also by the other diet options. That is, rats selected more fat and consumed more calories when chow was the alternative food than when separate sources of carbohydrate and protein were available.

Animals↗

Interrelationships between digestive proteolytic activities and production and quantitation of toxins in pseudomembranous colitis induced by Clostridium difficile in gnotobiotic mice.

Clostridium difficile pathogenicity is related to in vivo production of toxins, and it is of great interest to detect toxins produced in biological samples. Several reports have shown that proteases in stools interfere with immunological methods for quantitation of toxin A. The purpose of this work was to estimate the relationship between the proteases and the C. difficile toxins produced in a gnotobiotic mouse model of pseudomembranous cecitis. Cecal proteolytic activities hydrolyzed toxin A, and immunoglobulin G bound to the microtiter plate used in immunoassays. This interference could be blocked by the addition of trypsin inhibitor to the samples. The ability of soluble toxin A to bind to bound antibodies in an enzyme-linked immunosorbent assay was not affected by the proteases, but the biological activity was reduced 100-fold. The cytotoxicity of toxin B was not modified by proteolytic activity treatment. Mice inoculated with a low toxin A-producing strain of C. difficile did not died, and no modulation of proteolytic activities occurred. After inoculation with the lethal VPI strain of C. difficile, toxins A and B reached maximum levels in the ceca at 12 h postinfection. At this time, the proteolytic activities did not decrease from the levels seen at zero time. Mice died within 2 days. At this time (about 32 postinfection), proteolytic activities were sharply decreased in the lower parts of the digestive tracts. The findings that serum inhibited the proteases and that there was a 100-fold increase in serum-derived mouse immunoglobulins in the lumen as the C. difficile infection progressed suggest that the decrease in protease activity in the lower digestive tract may be related to the exudation of serum from the inflammation process.

Animals↗

Fixation of Clostridium difficile toxin A and cholera toxin to intestinal brush border membranes from axenic and conventional mice.

We have tested the in vitro binding of Clostridium difficile toxin A (enterotoxin) and cholera toxin to intestinal brush border membranes prepared from either conventional or axenic mice. Membranes from axenic mice were shown to be saturated at a lower toxin A concentration (at least 2.5 times lower). Because there were no significant differences between membranes from axenic and conventional mice in binding at low toxin A concentrations, the presence of the normal microflora seems to increase the number but not the affinity of brush border membrane receptors on the enterocyte surface. Corroborating the in vitro results, we observed that conventional mice were more sensitive to the pathological effects of toxin A given intragastrically than were axenic mice. In contrast, there was no difference in the binding characteristics of cholera toxin between membranes from conventional and axenic mice. We conclude that the presence of the mouse intestinal bacteria increases the number of C. difficile toxin A intestinal receptors but does not influence cholera toxin receptors.

Animals↗

Evolution of the caecal epithelial barrier during Clostridium difficile infection in the mouse.

The most striking effect of Clostridium difficile infection is its degrading of the intestinal barrier. The aim of this study is to establish whether the cellular or paracellular constituent of the barrier is the initial target of the toxins produced by C difficile. Accordingly, the caecal epithelium of C3H/He mice was challenged under three experimental conditions with the C difficile strain VPI 10463: (1) by in vivo inoculation of axenic mice, (2) by adding the toxins to ligated caeca in vivo, and (3) by adding them to the mucosal side of isolated caeca in Ussing chambers. Under all three conditions, the epithelial barrier was tested in caeca mounted in these chambers. The transepithelial potential difference (PD), electrical conductance (G), and intact and degraded Horseradish peroxidase (HRP) fluxes were used as indexes of permeability. Results were as follows: (1) In axenic mice, C difficile caused severe infection, produced toxins A and B, reduced PD, and enhanced G and intact HRP fluxes without changing degraded HRP fluxes, (2) four hours after the toxins were added to ligated caeca in vivo, PD was relatively unaltered, but G, and intact and degraded HRP fluxes increased, and (3) when toxins were added to caeca during two hours in the Ussing chambers, the only modification observed was an increase in degraded-HRP fluxes. These results indicate that the C difficile toxins gradually cause intestinal lesions. After an apparent resistance, they stimulate the endocytotic process and then increase paracellular permeability and finally cause loss of cell viability.

Animals↗

Polycose and sucrose appetite in rats: influence of food deprivation and insulin treatment.

Rats appear to have two different carbohydrate tastes, a sweet taste for sugars, and a "polysaccharide" taste for starch and starch-derived polysaccharides. The present study explored the possible functional significance of this dual taste system by comparing the effects of food deprivation and insulin treatment on the appetite for sucrose and Polycose. Food deprivation (24 h) produced comparable increases in the 5-min and 30-min intakes of Polycose and sucrose (1-8%) solutions in adult female rats. Polycose and sucrose intakes were also increased to a similar degree by insulin injections (1 unit/kg) during brief (3-min) one-bottle tests. In brief two-bottle tests, however, insulin treatment tended to shift the rat's preference from sucrose to Polycose. Chronic treatment with insulin increased the long-term intake of 30% Polycose and sucrose solutions, with the effect being more pronounced with Polycose. These findings demonstrate that energy deficit states enhance the appetite for Polycose as much as or more than the appetite for sucrose.

Animals↗

Spontaneous insulin fluctuations and the preabsorptive insulin response to food ingestion in humans.

Insulin secretion occurs in response to cephalic stimulation by foods; in humans, the response is quite variable and its importance in meal situations is difficult to assess. Insulinemia also varies spontaneously in the absence of food stimulation. In the present work, a comparative study of spontaneous and food-associated insulinemia changes was performed. Spontaneous preprandial fluctuations of glycemia and insulinemia were recorded and the presence of significant oscillations or trends was investigated. Premeal changes in insulinemia then served as a basis for evaluating the preabsorptive insulin response (PIR) during food ingestion. A sinewave fitted to preprandial insulin oscillations did not appear satisfactory as a basis for the assessment of the PIR. Significant PIRs were then defined in terms of deviation from a confidence interval (mean of the preprandial values +/- 2 SD). Significant PIRs were more frequent when the food presented was more palatable. Individual differences in responsiveness appeared. The physiological significance of a PIR over a background of spontaneous fluctuations is discussed.

Adult↗

The measurement of food preferences in humans: do taste-and-spit tests predict consumption?

Hedonic ratings of foods, obtained by laboratory taste-and-spit tests, are often used to determine the optimal concentration of sugar in a commercial food. However, the predictive value of these tests on actual consumption has not been demonstrated. Does the optimal sugar concentration in a specific food, as determined by a short exposure taste test, induce maximum intake of that food? In the present experiment, a standard food (yogurt) was presented in five sucrose concentrations (from 2% to 29%) to 18 subjects. The five types of yogurts were first tasted and rated for pleasantness. Secondly, they were presented in ad lib consumption tests. Discrepancies appeared between taste test ratings and ingestive responses, e.g., in subjects who preferred medium to high sucrose concentrations, the optimal concentration (in terms of intake) was lower than the "preferred" one (as determined by taste-and-spit tests). The results of taste-and-spit should be taken cautiously when trying to predict ingestion.

Adult↗