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C Besson

Publications and source records attributed to C Besson.

At least 19 recordsLinked to original sources

The bioavailability of polyphenols is highly governed by the capacity of the intestine and of the liver to secrete conjugated metabolites.

BACKGROUND: After ingestion of a complex meal containing foods and beverages of plant origin, different polyphenols are likely to be simultaneously present in the intestine. However, almost nothing is known about their interactions and possible consequences on their bioavailability. AIM OF THE STUDY: The present study deals with the intestinal absorption and splanchnic metabolism of three polyphenols, genistein, hesperetin and ferulic acid (FA),when perfused in the small intestine alone or in combination, at different doses (15 and 120 microM). METHODS: The fate of polyphenols in the small intestine was studied using a rat in situ intestinal perfusion model. Polyphenols were analysed in perfusate, bile and plasma by HPLC. RESULTS: Whatever the perfused dose, the efficiency of the net transfer towards the enterocyte was similar for the three polyphenols and not significantly modified by any association between these molecules. However, FA largely differed from the two flavonoids by its low intestinal secretion of conjugates. When perfused at 15 microM, the secretion of conjugates back to the lumen represented 6.2% of the net transfer into the enterocytes for FA compared to 25.5 and 20 % for genistein and hesperetin respectively. Intestinal conjugation and secretion of conjugates back to the gut lumen varied with the dose of flavonoids: saturation of conjugation was observed for the highest dose or when a high dose of a second flavonoid was perfused simultaneously. Intensity of the biliary secretion substantially differed among tested polyphenols: 7.7% of the net transfer for FA vs 50% for genistein or hesperetin. The extent of the enterohepatic cycling of these polyphenols was proportional to the perfused dose and unaffected by the simultaneous presence of different compounds in the intestine. CONCLUSION: Genistein and hesperetin appeared less available than FA for peripheral tissues because of a high intestinal and biliary secretion of their conjugates. Moreover, data suggest that a high polyphenol intake may improve their bioavailability due to saturation of the intestinal secretion of conjugates.

Animals↗

Determination of thiamine and its phosphate esters in rat tissues analyzed as thiochromes on a RP-amide C16 column.

A new reversed-phase chromatographic method is described for the separation and quantification of thiamine (T), thiamine monophosphate (TMP) and diphosphate (TDP) in rat tissues. Sample extraction with perchloric acid (HClO(4)) was found more suitable than extraction with trichloroacetic acid (TCA), as regards convenience and background fluorescence. Derivatization of thiamine vitamers to thiochromes was optimized and complete separation of TDP and TMP thiochromes was obtained on a RP-amide C16 column in isocratic elution, with T thiochrome eluting in less than 10 min. The precision and the accuracy of the HPLC procedure were assessed: ranging from 0.5 to 7.7% for intra-day and from 2.0 to 9.4% for inter-day precision, a recovery average of 101% was determined (range 90-111%). Mean values of recovery for TDP, TMP or T were 91, 96 and 90% for liver extracts, respectively. Analysis of vitamers in tissues of rat submitted to 8 days thiamin deficiency, followed by a 14 days repletion, showed a significant reduction of TPP after 8 days of depletion in liver (-67%), brains (-50%), kidneys (-60%), followed by a complete recovery upon repletion.

Animals↗

[Fibular tendon dislocations associated with calcaneal fractures: four case reports].

We report four cases of traumatic dislocation of the fibular tendons associated with calcaneal fractures. There are few reports of this type of association in the literature. We analyzed the diagnostic and therapeutic features. Two patients with a history of calcaneal fracture presented old, unrecognized, symptomatic dislocations of the fibular tendons. After CT confirmation, the tendons were repositioned surgically. During the last two years, CT scans performed systematically in patients with calcaneal fracture led to the discovery of two recent dislocations associated with calcaneal fractures. In these patients the fibular tendon dislocation was treated during the osteosynthesis procedure by relocating the tendon in the gutter and reinsertion of the retinaculum. The two older cases illustrated the serious functional consequences of neglecting displaced fibular tendons. We also detailed the characteristic CT signs observed with the two recent cases. The association of calcaneal fracture with fibular tendon displacement is rarely reported in the literature, but is not exceptional. Physical examination is limited during the acute phase. Imaging, particularly CT is required to demonstrate the tendon displacement. The objective results of surgical treatment were good. Orthopedic treatment is almost always unsuccessful. The association of fibular tendon displacement with calcaneal fracture is not exceptional. We have instituted a standardized CT protocol for all cases of calcaneal fracture in order to recognize disinsertion of the retinaculum and enable treatment at the same time as the osteosynthesis.

Adult↗

Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy.

HIV infection is associated with a high incidence of AIDS-related lymphomas (ARLs). Since the use of highly active antiretroviral therapy (HAART), the incidence of AIDS-defining illnesses has decreased, leading to a significant improvement in survival of HIV-infected patients. The consequences of HAART use on ARL are under debate. This study compared the incidence and the characteristics of ARL before and after the use of HAART in a large population of HIV-infected patients in the French Hospital Database on HIV (FHDH) and particularly in 3 centers including 145 patients with proven lymphoma. Within the FHDH, the incidence of systemic ARL has decreased between 1993-1994 and 1997-1998, from 86.0 per 10 000 to 42.9 per 10 000 person-years (P < 10(-30)). The incidence of primary brain lymphoma has also fallen dramatically between the periods, from 27.8 per 10 000 to 9.7 per 10 000 person-years (P < 10(-11)). The analysis of 145 cases of ARL in 3 hospitals showed that known HIV history was longer in the second period than in the first period among patients with systemic ARL (98 versus 75 months; P <.01). Patients had a higher number of CD4 cells at diagnosis during the second period (191 versus 63/microL, P = 10(-3)). Survival of patients with systemic ARL also increased between the periods (from 6 to 20 months; P =.004). Therefore, the profile of ARL has changed since the era of HAART, with a lower incidence of systemic and brain ARL. The prognosis of systemic ARL has improved.

Antiretroviral Therapy, Highly Active↗

[Adult T-cell leukemia/lymphoma. Clinical aspects].

BACKGROUND DATA: Adult T-cell leukemia/lymphoma (ATL) is a malignant proliferation of activated CD4+ T lymphocytes. The disease is almost exclusively found in patients living in retrovirus HTLV-1 endemic areas. VIROLOGY: In ATL, monoclonal HTLV-1 provirus is integrated into atypical lymphocytes, called clover-leaf lymphocytes. The pathogenic mechanism leading to HTLV-1-induced leukemogenesis remains obscure. The disease generally occurs after a long latency period. FOUR CLINICAL SUBTYPES: The diversity of the clinical presentation has led to the classification of ATL into four subtypes: acute or prototype, lymphoma, chronic, and painless. In the acute form of ATL there is a tumor syndrome associated with paraneoplastic hypercalcemia and a high rate of opportunistic infections due to the immunodepression predominated by cellular immunity. CLINICAL COURSE: Prognosis is poor for the acute and lymphomatous forms with a median survival of 6 and 10 months respectively. Infectious episodes are frequent, often caused by Pneumocystis carinii, and require systematic prophylaxis. Screening for anguilulosis and prophylaxis is also necessary.

Adult↗

[Adult T-cell leukemia/lymphoma. Therapeutic aspects].

CONVENTIONAL CHEMOTHERAPY: Complete remission of aggressive ATL (acute or lymphomatous forms) can be achieved in about 40% of the patients with conventional chemotherapy, but early relapse and infectious complications is the rule. For painless and chronic ATL, chemotherapy does not appear to be useful and can aggravate the immunodepression. NEW THERAPEUTIC APPROACHES: Encouraging results have been obtained with a combination regimen using an antiretroviral agent (AZT) and interferon alpha. Response rate has been high with good tolerance. In responders, the survival rate is better than with conventional chemotherapy. PERSPECTIVES: The success of a potentially antiretroviral approach for the treatment of this generally chemoresistant disease suggests that HTLV-1 virus could have a continuous effect on in vivo leukomogenesis.

Anti-HIV Agents↗

Incidence of hematological malignancies in Martinique, French West Indies, overrepresentation of multiple myeloma and adult T cell leukemia/lymphoma.

A registry of hematological malignancies is held in the unit of cytology of the University Hospital of Martinique. Human T cell lymphotropic virus type-1 (HTLV1) is endemic in this island. We determined the incidence and epidemiological features of hematological malignancies from the 715 new cases diagnosed between 1990 and 1998 among the adult population. Incidence rates per year were steady during this period. The most frequent hematological malignancies were multiple myeloma (MM) (34%), followed by non-Hodgkin's lymphoma (NHL) (23%). Among the cases of NHL with an immunohistological study, 57% had a T cell phenotype. Among these 61% were adult T cell leukemia/lymphoma. Epidemiological data on hematological malignancies in the West Indies has not been previously reported. There are two striking differences with other population-based registries: a high incidence of MM (5/100000) and a high proportion of T cell NHL among NHL (57%). The high proportion of T cell NHL is probably due to the high incidence of ATL. A low incidence of B cell NHL might also contribute to this effect. The increased incidence of MM in West Indies had not been previously reported. A similar high incidence of MM has been reported among Afro-Americans in the USA.

Adult↗

Bioavailability of phloretin and phloridzin in rats.

Phloretin is a flavonoid found exclusively in apples and in apple-derived products where it is present as the glucosidic form, namely, phloridzin (phloretin 2'-O-glucose). In the present study, we compared the changes in plasma and urine concentrations of these two compounds in rats fed a single meal containing 0.25% phloridzin or 0.157% phloretin (corresponding to the ingestion of 22 mg of phloretin equivalents). In plasma, phloretin was recovered mainly as the conjugated forms (glucuronided and/or sulfated) but some unconjugated phloretin was also detected. By contrast, no trace of intact phloridzin was detected in plasma of rats fed a phloridzin meal. These compounds presented different kinetics of absorption; phloretin appeared more rapidly in plasma when rats were fed the aglycone than when fed the glucoside. However, whatever compound was administered, no significant difference in the plasma concentrations of total phloretin were observed 10 h after food intake. At 24 h after the beginning of the meal, the plasma concentrations of phloretin were almost back to the baseline, indicating that this compound was excreted rapidly in urine. The total urinary excretion rate of phloretin was not affected by the forms administered, and was estimated to be 8.5 micromol/24 h in rats fed phloretin or phloridzin. Thus, 10.4% of the ingested dose was recovered in urine after 24 h.

Absorption↗

Class 2 resistant starches lower plasma and liver lipids and improve mineral retention in rats.

The effects of raw potato starch (RPS) and high amylose corn starch (HAS) on cecal digestion, lipid metabolism and mineral utilization (Ca and Mg) were compared in rats adapted to semipurified diets. The diets provided either 710 g wheat starch/100 g diet (control) alone or 510 g wheat starch/100 g diet plus 200 g resistant starch/100 g (RPS or HAS). Compared with rats fed the control diet, significant cecal hypertrophy (240% after 7 d of the fiber consumption) and short-chain fatty acids accumulation (especially propionic and butyric acids) occurred after both resistant starch diets. Apparent Ca, Mg, Zn, Fe and Cu absorptions were similarly enhanced by RPS and HAS (50, 50, 27, 21 and 90%, respectively). Cholesterol absorption was reduced to 14% of intake in rats fed RPS or HAS compared with 47% absorption in control rats. RPS and HAS were also effective in lowering plasma cholesterol (-31 and -27%, respectively) and triglycerides (-28 and -22%, respectively). There was no effect of the diets on cholesterol in d > 1.040 kg/L lipoproteins (HDL), whereas RPS and HAS depressed cholesterol in d < 1.040 kg/L lipoproteins (especially in triglyceride-rich lipoproteins). Moreover, there were lower concentrations of cholesterol (-50 and -40%, respectively) and triglycerides (-53 and -47%, respectively) in the livers of RPS- and HAS-fed rats. Thus, RPS and HAS have similar effects on intestinal fermentation, mineral utilization and cholesterol metabolism in rats.

Absorption↗

Catechin is metabolized by both the small intestine and liver of rats.

Flavan-3-ols are the most abundant flavonoids in the human diet, but little is known about their absorption and metabolism. In this study, the absorption and metabolism of the monomeric flavan-3-ol, catechin, was investigated after the in situ perfusion of the jejunum + ileum in rats. Five concentrations of catechin were studied, ranging from 1 to 100 micromol/L. The absorption of catechin was directly proportional to the concentration, and 35 +/- 2% of the perfused catechin was absorbed during the 30-min period. Effluent samples contained only native catechin, indicating that intestinal excretion of metabolites is not a mechanism of catechin elimination. Catechin was absorbed into intestinal cells and metabolized extensively because no native catechin could be detected in plasma from the mesenteric vein. Mesenteric plasma contained glucuronide conjugates of catechin and 3'-O-methyl catechin (3'OMC), indicating the intestinal origin of these conjugates. Additional methylation and sulfation occurred in the liver, and glucuronide + sulfate conjugates of 3'OMC were excreted extensively in bile. Circulating forms were mainly glucuronide conjugates of catechin and 3'OMC. The data further demonstrate the role of the rat small intestine in the glucuronidation and methylation of flavonoids as well as the role of the liver in sulfation, methylation and biliary excretion.

Animals↗

Comparison of the intestinal absorption of quercetin, phloretin and their glucosides in rats.

Absorption and metabolism of quercetin and isoquercitrin (quercetin 3-O-glucose) were investigated in rats after in situ perfusion of jejunum plus ileum (15 nmol/min) for 30 min and compared with those of phloretin and phloridzin (phloretin 2'-O-glucose). After perfusion of the glucosides, the corresponding aglycone forms and conjugated derivatives appeared in the lumen. The conjugated metabolites were similar to those recovered after intestinal perfusion of the aglycone forms. Regardless of the aglycone or glucoside perfused, only conjugated forms were present in the mesenteric vein blood draining the perfused segment showing the importance of intestinal conjugation. The hydrolysis of glucosides was a prerequisite step before their conjugation by intestinal enzymes and their transport towards the mucosal and serosal sides. In contrast to phloridzin, lactase phloridzin hydrolase activity did not seem to be an essential pathway for isoquercitrin hydrolysis. The 3-O-glucosylation of quercetin improved the net absorption of the aglycone (P < 0.05), whereas phloretin absorption decreased when present as 2'-O-glucoside (P < 0.05). Whatever the perfused compound, the efficiency of the absorption seemed to be linked to the intestinal conjugation process and to the luminal secretion of metabolites.

Animals↗

Cholesterol-lowering effects of guar gum: changes in bile acid pools and intestinal reabsorption.

Soluble fibers such as guar gum (GG) may exert cholesterol-lowering effects. It is generally accepted that bile acid (BA) reabsorption in portal blood is reduced, thus limiting the capacity of BA to down-regulate liver cholesterol 7alpha-hydroxylase, the rate-limiting enzyme of BA synthesis. In the present work, rats were adapted to fiber-free (FF) or 5% GG diets (supplemented or not with 0.25% cholesterol), to investigate various aspects of enterohepatic BA cycling. GG in the diet at a level of 5% elicited a significant lowering of plasma cholesterol during the absorptive period, in cholesterol-free (-13%) or 0.25% cholesterol (-20%) diet conditions. In rats adapted to the GG diets, the small intestinal and cecal BA pools and the ileal vein-artery difference for BA were markedly enhanced; reabsorption in the cecal vein was also enhanced in these rats. [14C]Taurocholate absorption, determined in perfused ileal segments, was not significantly different in rats adapted to the FF or GG diet, suggesting that a greater flux of BA in the ileum might support a greater ileal BA reabsorption in rats adapted to the GG diet. In contrast, capacities for [14C]cholate absorption from the cecum at pH 6.5 were higher in rats adapted to the GG diet than to the FF diet. Acidification of the bulk medium in isolated cecum (from pH 7.1 down to pH 6.5 or 5.8) or addition of 100 mM volatile fatty acids was also found to stimulate cecal [14C]cholate absorption. These factors could contribute to accelerated cecal BA absorption in rats fed the GG diet. The effects of GG on steroid fecal excretion thus appear to accompany a greater intestinal BA absorption and portal flux to the liver. These results suggest that some mechanisms invoked to explain cholesterol-lowering effect of fibers should be reconsidered.

Animals↗

Specificity of amygdalostriatal interactions in the involvement of mesencephalic dopaminergic neurons in affective perception.

We have recently shown that dopaminergic responses to an attractive or an aversive stimulus were respectively increased and decreased in the core part of the nucleus accumbens and the ventromedial dorsal striatum. By contrast, increases in dopaminergic responses were obtained in the shell part of the nucleus accumbens with stimuli of both affective values. In addition, the involvement of the basolateral amygdala in affective processes has been reported by several authors. Anatomo-functional relationships between the basolateral amygdala and striatal structures have also been described. Thus, in the present work we studied the regulation by the basolateral amygdala of affective dopaminergic responses in the two parts of the nucleus accumbens (core and shell) and the ventromedial dorsal striatum. More precisely, variations in extracellular levels of dopamine induced by an attractive or an aversive olfactory stimulus were studied using in vivo voltammetry in freely moving rats. Changes in dopamine levels in the three left striatal regions were measured after functional blockade of the ipsilateral basolateral amygdala with tetrodotoxin. Changes in place attraction or aversion toward the stimulus were studied in parallel to dopamine variations. The results obtained suggest a specific regulation of affective dopaminergic responses in the two parts of the nucleus accumbens by the basolateral amygdala and a lack of influence of the basolateral amygdala on the ventromedial dorsal striatum. The results suggest that attraction or aversion toward a stimulus are correlated with dopamine variations in the core of the nucleus accumbens and that the basolateral amygdala controls affective behavioural responses. These data may provide new insights into the pathophysiology of schizophrenic psychoses.

Affect↗

Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin's lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: a GELA study on 974 patients. Groupe d'Etudes des Lymphomes de l'Adulte.

BACKGROUND: Incidence of central nervous system (CNS) recurrence in patients with aggressive non-Hodgkin's lymphoma who did not receive meningeal prophylaxis is about 5%. Controversy remains regarding risk factors associated with such an event preventing a rational approach of prophylactic strategies. PATIENTS AND METHODS: We analyzed a cohort of 974 patients with aggressive lymphoma in complete remission (CR). All the patients received a CNS prophylaxis consisting of intrathecal injections and intravenous high-dose methotrexate. The risk repartition on the basis of the international prognostic index (IPI) of these 974 CR-patients was low (L): 41%, low-intermediate (LI): 27%, high-intermediate (HI): 19%, high (H): 13%. RESULTS: The incidence of isolated CNS relapse was 1.6%. In a first multivariate logistic regression analysis an increased LDH (P = 0.05, RR = 5) and the presence of more than one extranodal site (P = 0.05, RR = 3) were identified as independent risk factors for isolated CNS relapse. Another multivariate analysis incorporating IPI as a unique parameter showed that only IPI remained significantly associated with a higher risk of CNS relapse (L-LI: 0.6% vs. HI H: 4.1%, P = 0.002; RR = 7). CONCLUSION: Prophylaxis notably reduces the risk of CNS recurrence in the higher risk patients. By contrast, we propose the deletion of prophylactic intrathecal injections in the lower risk patients.

Antimetabolites, Antineoplastic↗

Dipeptide derivative synthesis catalyzed by Pseudomonas aeruginosa elastase.

Pseudomonas aeruginosa elastase was used to synthesize various N-protected dipeptide amides. The identity of the products was confirmed by FAB(+)-MS. After recrystallization, the yield of their synthesis was calculated, their purity was checked by RP-HPLC and their melting point was measured. With regard to the hydrolysis, it is well-established that the enzyme prefers hydrophobic amino acids in P'1 position and it has a wide specificity for the P1 position. This specificity was demonstrated to be quite unchanged when comparing the initial rates of peptide bond formation between different carboxyl donors (Z-aa) and nucleophiles (aa-NH2). The elastase, but not the thermolysin, was notably able to incorporate tyrosine and tryptophan in P'1 position. Furthermore, synthesis initial rates were at least 100 times faster with the elastase. To overcome the problematic condensation of some amino acids during chemical peptide synthesis, it has been previously suggested that enzymatic steps can combine with a chemical strategy. We demonstrated that the elastase readily synthesizes dipeptide derivatives containing various usual N-protecting groups. It was especially able to condense phenylalaninamide to Fmoc- and Boc-alanine. Increasing interest in peptides containing unnatural amino acids led us to try the elastase-catalyzed synthesis of Z-dipeptide amides including those amino acids in the P1 position. A synthesis was demonstrated with alphaAbu, Nle, Nva and Phg.

Catalysis↗

Part of quercetin absorbed in the small intestine is conjugated and further secreted in the intestinal lumen.

Rutin and quercetin absorption and metabolism were investigated in rats after in situ perfusion of jejunum plus ileum (15 nmol/min). In contrast to rutin, a high proportion of quercetin (two-thirds) disappeared during perfusion, reflecting extensive transfer into the intestinal wall. Net quercetin absorption was not complete (2.1 nmol/min), inasmuch as 52% were reexcreted in the lumen as conjugated derivatives (7.7 nmol/min). Enterohepatic recycling contribution of flavonoids was excluded by catheterization of the biliary duct before perfusion. After a 30-min perfusion period, 0.71 microM of quercetin equivalents were detected in plasma, reflecting a significant absorption from the small intestine. The differential hydrolysis of effluent samples by glucuronidase and/or sulfatase indicates that the conjugated forms released in the lumen were 1) glucuronidated derivatives of quercetin and of its methoxylated forms (64%) and 2) sulfated form of quercetin (36%). In vitro quercetin glucuronides synthetized using jejunal and ileal microsomal fractions were similar to those recovered in the effluent of perfusion. These data suggest that glucuronidation and sulfatation take place in intestinal cells, whereas no glucurono-sulfoconjugates could be detected in the effluent. The present work shows that a rapid quercetin absorption in the small intestine is very effective together with its active conjugation in intestinal cells.

Animals↗