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Biomedical subjects

F Lucas

Publications and source records attributed to F Lucas.

At least 19 recordsLinked to original sources
PubMed2001

A therapeutic area review of oncology products and players.

This article reviews the dynamics of the oncology market and treatment trends and provides strategic guidance to those concerned with new product discovery and development. Cancer is the therapeutic area of highest potential, with an annual market value expected to be in excess of US 40 billion dollars in 2020. The global incidence of cancer cases is forecast to more than double over the next 20 years. Investments in research and development will keep pace with the growing demand for effective treatments, aiming to fulfil the many and often discrete unmet medical needs. Recent breakthroughs promise more successful outcomes, particularly with the advent of more selective chemotherapy and novel therapeutic approaches. Among the latter, a number of angiogenesis inhibitors and monoclonal antibodies (mAbs) should show encouraging levels of efficacy by 2004. Oncology is a complex and high-risk therapeutic area that offers high rewards. It is appropriate for only the stronger or more focused serious players within the pharmaceutical industry. The winners will be the companies with a long-term strategic intent, a credible portfolio and engagement in appropriate alliances, particularly in discovery. The future presents ethical, clinical and commercial challenges, given the wide disparity of therapeutic outcomes among cancer patients around the world. The real success will thus be to treat cancer in innovative ways that benefit everyone and are, in volume and across the life cycle, commercially attractive to the treatment provider.

Journal Article↗
PubMed2000

Effects of ammonia and amino acids on the growth and proteolytic activity of three species of rumen bacteria: Prevotella albensis, Butyrivibrio fibrisolvens, and Streptococcus bovis.

The addition of increasing physiological concentrations of ammonia or amino acids had distinct effects on the growth and proteolytic activity of Streptococcus bovis JB1, Prevotella albensis, and Butyrivibrio fibrisolvens DSM3071. The growth of S. bovis and B. fibrisolvens was enhanced by NH(3) and AA, and that of P. albensis was reduced compared with a control with protein as the sole source of nitrogen. The proteolytic activity of S. bovis and P. albensis was reduced, but that of B. fibrisolvens was improved. NH(3) seemed to act mainly on the cell-associated fraction of the proteolytic activity, while the action of AA was not specific. In the rumen the proteolytic activity of S. bovis and P. albensis would be optimal at low concentrations of NH(3) or AA (<0.05 and <0.27 g/L respectively). In contrast, B. fibrisolvens would need higher concentrations (0.5 g/L of NH(3) or 2.7 g/L of AA). It can be assumed that these bacteria will grow in different ecological niches.

Amino Acids↗
PubMed2000

[Multiple cutaneous reticulohistiocytosis].

BACKGROUND: Multicentric reticulohistiocytosis is a non Langerhans cell histiocytosis. This rare disease is characterized by cutaneous papules and nodules and a destructive polyarthritis; multisystem involvement may occur. Multiple and diffuse cutaneous reticulohistiocytosis have been more rarely reported. We present a case which was distinctive by the existence of multiple cutaneous plaques. CASE REPORT: A 65-year-old woman presented cutaneous papules and nodules associated with a destructive arthritis affecting the hands. Histological examination of a cutaneous biopsy associated with immunophenotyping and electronic microscopy permitted us to make the diagnosis of multicentric reticulohistiocytosis. The search for visceral involvement or underlying neoplasia was negative. Rapidly, cutaneous aggravation occurred with multiple and diffuse infiltrated plaques on the back, the face, the ears, the thighs and the forearms. The same histological aspect was found for these lesions. Treatment with corticosteroids and cyclophosphamide was successful. DISCUSSION: This case report is the first one with diffuse cutaneous lesions of multicentric reticulohistiocytosis with aspect of infiltrated plaques. Diffuse cutaneous lesions in multicentric reticulohistiocytosis have been rarely reported with diffuse papules or nodules pattern. A visceral involvement seems to be more frequent for diffuse cutaneous involvement. In all cases, the association of multicentric reticulohistiocytosis with neoplasia in up to 25 p. 100 is of interest. Treatment of multicentric reticulohistiocytosis consists in corticosteroids at the initial phase associated with alkylants agents or methotrexate.

Aged↗
PubMed1999

Flavor preferences conditioned by high-fat versus high-carbohydrate diets vary as a function of session length.

Intragastric (i.g.) infusions of fat and carbohydrate condition flavor preferences in rats, but different results have been obtained in studies using pure and mixed nutrient infusions. This experiment compared the preference conditioning effects of mixed high-carbohydrate (HC) and high-fat (HF) diet infusions during short-term and long-term sessions. In Experiment 1 food-deprived rats were given one flavored saccharin solution (CS+HC) paired with i.g. infusions of an HC liquid diet, a second flavor (CS+HF) paired with HF diet infusions, and a third flavor (CS-) paired with i.g. water infusions during 30-min one-bottle training sessions. In subsequent two-bottle tests (30 min/day), the rats preferred both CS+s to the CS- and preferred the CS+HC to the CS+HF. In Experiment 2, the same rats were trained and tested with the CSs and paired infusions during 22 h/day sessions with chow available ad lib. Both CS+s were again preferred to the CS-, but now the CS+HF was preferred to the CS+HC. When given additional 30-min choice sessions in Experiment 3 the rats showed no reliable preference for the CS+HC versus CS+HF under food-deprived or ad lib conditions. In Experiment 4, the rats were given 22-h CS+HC versus CS+HF choice sessions every other day. They showed no reliable CS preference during the first 30 min of each session, but reliably preferred the CS+HF during the remaining 21.5 h. These findings indicate that previously reported differences in preferences conditioned by pure versus mixed nutrient infusions are due to training procedures (session length, deprivation state) rather than to the type of nutrient infusions per se. The rats displayed different CS+HF versus CS+HC preferences as a function of test duration even after being given both short- and long-term training. Thus, short-term choice tests do not always predict the long-term intakes and preferences for high-fat and high-carbohydrate foods.

Animals↗
PubMed1999

Differential reinforcing and satiating effects of intragastric fat and carbohydrate infusions in rats.

Food intake and preferences are modulated by the postingestive satiating and reinforcing actions of nutrients. This experiment compared the feeding effects of isocaloric intragastric (i.g.) carbohydrate (maltodextrin) and fat (corn oil) infusions in food-restricted rats fed low-fat (12% fat kcal) or high-fat (48% fat kcal) diets. In Experiment 1, the rats were given one flavored saccharin solution (CS+C) paired with i.g. carbohydrate infusions, a second flavor (CS+F) paired with i.g. fat infusions, and a third flavor (CS-) paired with i.g. water infusions during 30-min one-bottle training sessions. In subsequent two-bottle tests, the rats preferred both CS+s to the CS- (68-83%) and the CS+C to the CS+F (68-70%). In Experiment 2, the feeding inhibitory effects of the nutrient infusions on an ongoing meal (satiation test) or a subsequent meal (satiety test) were compared. The intake of a palatable Polycose+saccharin solution was suppressed by a concurrent carbohydrate infusion but not by a fat infusion. Also, i.g. carbohydrate preloads suppressed the intake of a subsequent (30-180 min) mixed carbohydrate+fat test meal more than did i.g. fat preloads. The satiety effects of the fat preloads were more pronounced in rats fed the low-fat diet than in rats fed the high-fat maintenance diet. Diet composition did not reliably influence the preference conditioning and satiation effects of the nutrient infusions. These results confirm prior reports that fat is less satiating than carbohydrate, and further demonstrate that i.g. carbohydrate infusions condition a stronger flavor preference than fat infusions.

Analysis of Variance↗
PubMed1999

Combination of biomolecular and stable isotope techniques to determine the origin of organic matter used by bacterial communities: application to sediment.

Natural isotopic composition is a good tool to trace organic matter in ecosystems. Recent studies used a combination of molecular and stable isotope techniques to determine the origin of the organic carbon used by bacteria in the water column. In our study, we show that this procedure can be used for analysis of sediment bacterial communities with few modifications. In the water column, bacterial recovery is done before DNA extraction. In the sediment, we tested qualitatively and quantitatively a direct and indirect extraction of DNA. The direct extraction was the most efficient. It recovered between 3.1 and 15.8 microg DNA g(-1) dry sediment and the contamination of field samples by eucaryotic DNA was less than 13%. In this preliminary study of the salt marsh ecosystem, the delta(13)C values of DNA (-26 to - 24%) recovered from the sediment were close to the delta(13)C values of halophytic plants (-26.4 and - 25.3%) showing a relationship between plants and microorganisms. Thus, this procedure can be used to trace the flow of carbon through the sediment microbial biomass and to understand the variation of bacterial activity according to the inputs of allocthonous and autochtonous organic matter.

Bacteria↗
PubMed1998

Increased flavor acceptance and preference conditioned by the postingestive actions of glucose.

In Experiment 1, rats were given daily 2-h access to chow and water and 20-h access to flavored solutions (cherry or grape). On alternate days, one flavor (CS+) was paired with intragastric infusions of 16% glucose and another flavor (CS-) with IG water. In subsequent choice tests, the rats strongly preferred (95%) the CS+ to the CS-. CS+ intake also greatly exceeded CS- intake during one-bottle training sessions (71 vs. 18 g/20 h). This increased acceptance was due to both increased bout size and number. When CS+ was paired with IG water (extinction test), CS+ bout size declined to CS- levels, while CS+ bout number and total intake remained elevated. In Experiment 2, rats trained with sucrose octa acetate and citric acid solutions also showed increased CS+ acceptance and preference in one- and two-bottle tests, respectively. The rats also consumed more CS+ than CS- during short-term (30 min/day) one-bottle tests and intraoral intake tests under both deprived and ad lib. feeding conditions. These results demonstrate that the postingestive actions of glucose can condition substantial increases in flavor acceptance as well as flavor preference.

Animals↗
PubMed1998

Devazepide, a CCK(A) antagonist, attenuates the satiating but not the preference conditioning effects of intestinal carbohydrate infusions in rats.

Endogenous cholecystokinin (CCK) is thought to participate in the satiating action of foods, and some data suggest that it may also mediate their postingestive reinforcing effects. This was investigated by determining if the CCK(A) receptor antagonist, devazepide, attenuates flavor preference conditioning by intraduodenal (I.D.) carbohydrate infusions. In Experiment 1, food-restricted female rats were trained 30 min/day to associate a cue flavor (CS+) with I.D. infusions of 8% Polycose and a different flavor (CS ) with I.D. water infusions. Half of the rats (DEV group) were pretreated with devazepide (300 microg/kg body weight) and the other half (CON group) with vehicle, 30 min prior to CS training sessions and choice tests. Both groups displayed similar CS+ preferences (CON: 68%; DEV: 69%). In contrast, devazepide blocked the feeding inhibitory effects of I.D. Polycose infusion and cholecystokinin octapeptide injection in Experiment 2. A higher dose of devazepide (1200 microg/kg) also failed to inhibit preference conditioning by I.D. Polycose in Experiment 3. These results indicate that, although CCK(A) mechanisms play a role in the satiating effect of I.D. carbohydrates, they do not mediate their reinforcing effect. The present study, along with other recent reports, indicate that different mechanisms mediate the satiating and reinforcing actions of nutrients.

Animals↗
PubMed1998

High-fat diet preference and overeating mediated by postingestive factors in rats.

The role of postingestive factors in the preference for and overconsumption of high-fat (HF) foods, relative to high-carbohydrate (HC) foods, was investigated using a self-regulated intragastric feeding procedure. On one-bottle training days, rats drank one flavored saccharin solution [conditioned stimulus (CS) + HF] paired with intragastric infusions of an HF liquid diet, a second flavored solution (CS+HC) paired with an HC liquid diet, and a third flavored solution (CS-) paired with intragastric water. The diets had the same energy and protein content; the CS solutions and infusions along with chow were available ad libitum. The rats drank more CS and self-infused more diet on HF than HC training days. In two-bottle choice tests, the rats preferred the CS+HF to the CS+HC and both CS+HF and CS+HC to the CS-. The rats consumed more CS+HF than CS+HC by taking more bouts per day; bout sizes did not reliably differ. In a subsequent experiment, rats preferred the CS+HF even though diet intakes in training were matched. In a final experiment, the CS+HC and CS+HF intakes were equated in training by diluting the HC diet. Now the rats did not reliably prefer the CS+HF to the CS+HC, yet caloric intakes were much higher on CS+HF than CS+HC training days. Thus, relative to an isocaloric HC diet, the postingestive effects of HF diets stimulate overeating and condition a stronger flavor preference. Reduced satiety rather than increased reinforcement may be the direct promoter of overeating. However, postingestive reinforcement may enhance the selection of HF foods when a choice of HF and HC foods is available.

Animals↗
PubMed1997

Flavor preferences conditioned by intragastric polycose in rats: more concentrated polycose is not always more reinforcing.

Prior studies have obtained conditioned preferences for flavors paired with intragastric (IG) infusions of Polycose (hydrolyzed starch) at concentrations of 1-32% over a different flavor paired with IG water. The present study determined if rats would also learn to prefer a flavor paired with concentrated Polycose infusion over a flavor paired with a more dilute Polycose infusion. In Experiment 1, adult female rats were food-deprived and trained during alternating one-bottle sessions (30 min/day) to associate one flavored solution (the CS + 8) with IG infusions of 8% Polycose, a second flavored solution (the CS + 16) with IG infusions of 16% Polycose, and a third flavored solution (the CS-) with IG water infusions. In subsequent choice tests, the rats displayed similar preferences for the CS + 8 and CS + 16 over the CS-, but preferred the CS + 16 to CS + 8 in a direct choice test. A similar preference pattern was obtained in 22 h/day tests with the rats nondeprived. In Experiment 2, new rats were similarly trained and tested but with CS + 16 and CS + 32 solutions paired with 16% and 32% Polycose infusions, respectively. The rats preferred both CS+ solutions over the CS- solution in the short- and long-term tests. However, the CS + 16 was preferred over the CS + 32 by the food-deprived rats in the short-term tests. The two CS+ solutions were equally preferred in the long-term tests with food ad lib. These and other findings indicate that the postingestive reinforcing action of Polycose increases as concentration increases from 1% to 16% but does not increase further, and may actually decrease, at a 32% concentration. The rapid satiating effect of concentrated carbohydrate solutions may limit their reinforcing consequences.

Administration, Oral↗
PubMed1997

Relative validity and reproducibility of a French dietary history questionnaire.

BACKGROUND: A self-administered dietary history questionnaire, especially developed for use in a large French prospective cohort study, was tested for accuracy of food intake measurement by comparing it to the average of 9-12 24-hour recalls. This questionnaire was structured according to the French meal pattern. An important feature of the questionnaire was the separation into a quantification part and qualification part. The first part quantifies consumption by frequency and portion sizes per food group or food item. The second part provides more detailed qualitative information on separate items within one food group. The total number of food items in the questionnaire was 238. METHODS: The questionnaire was administered twice to 119 study subjects, with an interval of approximately one year (1990-1991). During that year, 24-hour recalls were carried out monthly. Reproducibility and relative validity of the questionnaire were assessed. RESULTS: The correlation coefficients for reproducibility ranged from 0.40 to 0.74 for foods and from 0.54 to 0.75 for nutrients. The correlation coefficients for relative validity ranged from 0.10 to 0.71 for foods and from 0.29 to 0.81 for nutrients (adjustment for total energy and attenuation for nutrients). Percentage of subjects classified in the same or adjacent quintile by questionnaire as well as by 24-hour recall was on average 76% for foods and 72% for nutrients. CONCLUSIONS: These data indicate that this questionnaire can be used to classify study subjects according to their food or nutrient intake over a one-year period, within a known degree of precision.

Adult↗
PubMed1996

The composition of the maintenance diet alters flavor-preference conditioning by intragastric fat infusions in rats.

Prior studies indicate that intragastric (IG) fat infusions condition only weak flavor preferences in chow-fed rats using brief daily training sessions. The present study attempted to facilitate fat conditioning by feeding rats a high-fat maintenance diet or by adding an oily flavor to the conditioning stimuli. In Experiment 1, rats were fed restricted rations of either a chow-corn oil mixture (48% energy as fat, HF group) or regular chow (12% fat, LF group). During 1-bottle training sessions, drinking a flavored (CS+, e.g., cherry) saccharin solution was paired with IG fat (7.1% corn oil emulsion). On other days, an alternate flavor (CS-, e.g., grape) was paired with IG water. In subsequent 2-bottle tests between the CS+ and CS- flavors, the HF rats displayed a stronger CS+ preference than the LF rats (90% vs. 62%). Experiment 2 tested the effect of a semisynthetic HF maintenance diet (48% fat energy), using a conditioning procedure similar to that of Experiment 1. The rats displayed only a moderate (72%) CS+ preference. When switched to the chow-oil maintenance diet and retrained with new CS flavors, they developed a 90% CS+ preference. In Experiment 3, chow-fed rats were trained and tested with oily CSs (i.e., 2% corn oil was added to flavored saccharin solutions). They failed to show a preference for the CS+ paired with IG oil. Thus, increasing the level of fat in the maintenance diet can greatly enhance preference conditioning with IG fat, but the amplitude of the effect is influenced by the composition of the high-fat food. In contrast, adding a fatty flavor to the conditioning stimuli did not improve fat conditioning.

Animals↗
PubMed1996

Abdominal vagotomy does not block carbohydrate-conditioned flavor preferences in rats.

The effects of abdominal vagotomy on the flavor preferences conditioned by Polycose (a maltodextrin) were investigated in female rats. Using an oral-delay training method, a modest conditioned flavor preference (67%) was obtained in control rats but not in rats with subtotal abdominal vagotomy (hepatic branch intact). The rats were fed a chow diet, and gastric stasis in the vagotomized rats may have interfered with preference learning. To facilitate conditioning, the rats were switched to a liquid maintenance diet and trained with new flavors paired with intragastric (IG) infusions of Polycose and water. With this procedure, the vagotomized and control rats acquired strong preferences (83-88%) for the flavor paired with IG Polycose. In a second experiment, flavor preferences conditioned by IG Polycose were obtained in rats with total abdominal vagotomy although the preference was attenuated relative to control rats (79% vs. 97%). Gastric motor problems (dumping) may have been a factor because the vagotomized rats consumed much less flavored solution (and therefore received less IG Polycose) during training than did controls. These findings indicate that an intact vagus nerve is not necessary to obtain carbohydrate-conditioned preferences, although vagotomy may interfere with the conditioning in some experimental situations.

Animals↗
PubMed1996

Food deprivation increases the rat's preference for a fatty flavor over a sweet taste.

Previous research indicates that food deprivation increases the rat's preference for high-fat over low-fat foods. Since these foods differ in their flavors and post-ingestive effects, both factors may be implicated. The present study investigated preferences in food deprived and non-deprived rats using non-nutritive mineral oil emulsion (MO) and saccharin solution (SAC), which have a fatty flavor and sweet taste, respectively. The deprived rats consumed more MO than SAC in one- and two-bottle tests, while the non-deprived rats ingested as much SAC as MO in one-bottle tests and preferred SAC in two-bottle tests. Several aspects of the data suggest that the deprivation-related shift in preference between MO and SAC was determined by changes in long-term energy balance. A follow-up conditioning experiment discarded the possibility that the observed preference shift was related to differential reinforcing effects of the two substances. In conclusion, long-term food restriction increases the preference for an oily flavor over a sweet taste via a mechanism that does not involve nutritive feedback. It remains to be determined to what extent this alternation in flavor preference influences food selection when post-ingestive nutritive feedback can influence food choice.

Animals↗
PubMed1996

Capsaicin attenuates feeding suppression but not reinforcement by intestinal nutrients.

During and after a meal, the presence of nutrients in the intestine can be rapidly detected and signaled to the brain via visceral afferents. Intestinal infusions of carbohydrate and fat suppress food intake, and this satiety action is inhibited by capsaicin, a neurotoxin that produces a partial visceral deafferentation. This study determined if the postingestive reinforcing action of nutrients is also suppressed by capsaicin treatment. Food-restricted control and capsaicin-treated rats were trained to drink a flavored solution paired with intraduodenal infusions of carbohydrate (Polycose solution) on some days and, on other days, a differently flavored solution paired with intraduodenal water infusions. In a choice test, both groups displayed a strong preference for the Polycose-paired flavor. In a subsequent satiety test, however, intraduodenal Polycose suppressed sucrose sham feeding in the controls but not in capsaicin-treated rats. The same rats were next trained to associate new flavors with intraduodenal fat (corn oil emulsion) and intraduodenal water infusions. During training, oil infusions reduced oral intakes in the controls much more than in the capsaicin-treated rats. Both groups reliably preferred the oil-paired flavor in the subsequent choice test. These results indicate that, unlike the satiating effect of intestinal carbohydrate and fat, the reinforcing actions of these nutrients are not mediated by capsaicin-sensitive visceral afferents. The data also imply that the postingestive reinforcement produced by nutrients is not dependent on the nutrients' satiating quality.

Animal Nutritional Physiological Phenomena↗
PubMed1996

The importance of taste and palatability in carbohydrate-induced overeating in rats.

Rats offered a carbohydrate solution (sugar or polysaccharide) in addition to chow typically overeat and gain excessive weight. The present study sought to determine if the palatable taste of these solutions contributes to the overeating response. Adult female rats were fitted with chronic intragastric catheters and given ad libitum access to chow and a drinking fluid that was paired with intragastric infusions. For one group (P + S), the flavored solution was a highly preferred mixture of 2% Polycose and 0.2% saccharin paired with intragastric infusions of 30% Polycose. For a second group (SOA), the flavored solution (0.03% sucrose octaacetate) had unpreferred bitter taste and was paired with intragastric infusions of 32% Polycose. Thus both groups were effectively exposed to the postingestive effects of 32% Polycose but paired with a palatable (P + S) or unpalatable (SOA) flavor. A control group had water to drink paired with intragastric water infusions. During the 4-wk experimental period, the P + S group consumed 34% more total energy (chow + Polycose) and gained more weight than did the SOA and control groups. The P + S group also consumed substantially more flavored solution and more energy as Polycose compared with the SOA group. The SOA group did not gain reliably more weight than the control group, although their total energy intake was 13% higher than that of the controls. In a choice test conducted at the end of the experiment, the P + S group displayed a strong preference (98%) for the Polycose + saccharin solution over water. In contrast to the control group, which avoided the SOA solution relative to water, the SOA group preferred the SOA solution (71%) confirming prior reports of Polycose-conditioned SOA preferences. These results demonstrate that palatability has a major effect on the overeating and obesity produced by carbohydrate solutions. In the absence of a highly preferred taste, the postingestive actions of Polycose produce only a small hyperphagic effect and no excess weight gain.

Animals↗
PubMed1995

Carbohydrate, fat, and protein condition similar flavor preferences in rats using an oral-delay procedure.

Flavor preferences conditioned by carbohydrate (Polycose), protein (casein hydrolysate), and fat (corn oil) were compared using an oral-delay training method. In Experiment 1 separate groups of food deprived rats were trained to associate a CS+ flavor (e.g., grape-saccharin) with the delayed (10 min) presentation of isocaloric carbohydrate, protein, or fat sources. A CS- flavor (e.g., cherry-saccharin) was paired with the delayed presentation of an unflavored saccharin solution. In subsequent two-bottle tests the carbohydrate, protein, and fat trained groups displayed significant preferences for the CS+ over the CS-. In Experiment 2 each rat was trained to associate two new flavors with two of the three nutrients (e.g., orange with carbohydrate, and strawberry with protein). In subsequent two-bottle tests the rats equally preferred the two nutrient-paired flavors. Experiment 3 compared the preferences for the new CS+ flavors vs. the original CS-flavor. The rats displayed similar preferences for carbohydrate-, protein- and fat-paired CS+ over the CS-. The similar preferences obtained with the three different nutrients support the view that preference conditioning is mediated by the nutrients' caloric value. Other studies suggest, however, that nutrient-specific signals are also involved in the conditioning process.

Animals↗