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Biomedical subjects

Robert Benamouzig

Publications and source records attributed to Robert Benamouzig.

At least 19 recordsLinked to original sources

Celecoxib leads to G2/M arrest by induction of p21 and down-regulation of cyclin B1 expression in a p53-independent manner.

A unique in vitro system has been developed in our lab that consists of normal enterocytes derived from the rat ileum (IEC-18 cells) and their transformed derivatives with c-K-ras (R1 cells), anti-sense bak (B3 cells) and cyclin D1 (D1 cells). R1 and B3 cells express high level of COX-2 protein and PGE2. IEC 18 and D1 cells express negligible amount of COX-2, and produce very low level of PGE2. A relatively low dose of celecoxib (5-10 microM) induced G2/M arrest, followed by induction of apoptosis in the transformed but not in the normal cells. Down-regulation of cyclin B1 and up-regulation of p21 expressions independent of p53 might have cause this cell cycle block. Growth inhibition was related to COX-2 function with 90-95% reduction in PGE2 production. These findings may be of clinical importance, since low concentration of celecoxib can be achieved in human serum following standard anti-inflammatory (100-200 mg bid) regime.

Animals↗

[Treatment of super super morbid obesity by sleeve gastrectomy].

UNLABELLED: INTEREST OF WORK: The longitudinal or "sleeve" gastrectomy was recently introduced into the therapeutic arsenal of the bariatric surgeon. It is a restrictive procedure that reduces stomach capacity by 75%. We present here a preliminary experience with four patients. METHODS: Four patients with super super obesity (body mass index (BMI)>60 kg/m2) underwent longitudinal or "sleeve" gastrectomy. Their average preoperative weight was 173 kg (range: 147-190 kg) and mean BMI 65 kg/m2 (range: 61-67 kg/m2). RESULTS: The average post-operative follow-up was 6 months (range: 2-12 months). Average weight loss at 6 months was 40 kg (range: 20-60 kg) and average decrease in BMI at 6 months 16.3 kg/m2 (range: 6-23 kg/m2). We noted a postsurgical complication in only one patient (subdiaphragmatic abscess treated with drainage). PERSPECTIVES: These preliminary results suggest that the sleeve gastrectomy is associated with few perioperative complications and offers rapidly effective treatment for super super morbid obesity. Long-term results require further investigation.

Adult↗

Compared with casein or total milk protein, digestion of milk soluble proteins is too rapid to sustain the anabolic postprandial amino acid requirement.

BACKGROUND: The in vivo quality of milk protein fractions has seldom been studied in humans. OBJECTIVE: Our objective was to compare the postprandial utilization of dietary nitrogen from 3 [(15)N]-labeled milk products: micellar caseins (MC), milk soluble protein isolate (MSPI), and total milk protein (TMP). DESIGN: The macronutrient intakes of 23 healthy volunteers were standardized for 1 wk, after which time the subjects ingested a meal containing MC (n = 8), MSPI (n = 7), or TMP (n = 8). [(15)N] was measured for an 8-h period in plasma amino acids, proteins, and urea and in urinary urea. RESULTS: The transfer of dietary nitrogen to urea occurred earlier after MSPI ingestion than after MC and TMP ingestion, and concentrations remained high for 8 h, concomitantly with higher but transient hyperaminoacidemia and a higher incorporation of dietary nitrogen into plasma amino acids. In contrast, deamination, postprandial hyperaminoacidemia, and the incorporation of dietary nitrogen into plasma amino acids were lower in the MC and TMP groups. Finally, total postprandial deamination values were 18.5 +/- 2.9%, 21.1 +/- 2.8%, and 28.2 +/- 2.9% of ingested nitrogen in the TMP, MC, and MSPI groups, respectively. CONCLUSIONS: Our results confirm the major role of kinetics in dietary nitrogen postprandial utilization and highlight the paradox of MSPI, which, despite its high Protein Digestibility Corrected Amino Acid Score, ensures a rate of amino acid delivery that is too rapid to sustain the anabolic requirement during the postprandial period. Milk proteins had the best nutritional quality, which suggested a synergistic effect between soluble proteins and caseins.

Adult↗

Postprandial metabolic utilization of wheat protein in humans.

BACKGROUND: The quality of cereal protein has been little studied in humans despite its quantitative importance in the diet, particularly in developing countries. OBJECTIVE: The objective of this study was to determine the nutritional value of wheat protein in humans as assessed by the measurement of their real ileal digestibility and postprandial retention. DESIGN: Healthy young adults (n = 14) were fitted with an intestinal tube to allow the collection of intestinal fluid in the duodenum or terminal ileum. Subjects received a mixed meal of 136 g wheat toast that contained 24.6 g uniformly and intrinsically [(15)N]-labeled wheat protein. Intestinal fluid, blood, and urine were collected for 8 h postprandially. RESULTS: The real ileal digestibility of dietary wheat nitrogen amounted to 90.3 +/- 4.3%. The cumulative amount of dietary nitrogen transferred to the deamination pools reached a plateau at 8 h of 24.7 +/- 6.8% of the amount ingested. The urinary excretion of dietary nitrogen in ammonia was high (0.8 +/- 0.3% of ingested dose). The incorporation of dietary nitrogen into serum protein reached 7.0 +/- 1.9% of the meal. Postprandial wheat protein retention was 66.1 +/- 5.8%. CONCLUSIONS: Our results show that wheat proteins had the same true ileal digestibility as did most of the plant proteins already studied in humans, but also that they had a lower postprandial nitrogen retention value. However, this low value was higher than that predicted from the calculation of indispensable amino acid scores, ie, 89% rather than 30-40% of the nutritional value of milk proteins.

Adult↗

Low dose aspirin, COX-inhibition and chemoprevention of colorectal cancer.

Chemoprevention of colorectal cancer involves the long-term use of pharmacologic agents that can prevent neoplasms from developing in the large bowel. This new approach requires major funding and human investments. Among the most widely studied agents for the chemoprevention of colorectal cancer, aspirin, the NSAIDs and COX-2 inhibitors seem to be the most promising. A large number of observational epidemiological studies show that regular use of aspirin and other NSAIDs is associated with a reduction in the risk of developing both colorectal adenomas and cancer. In addition, the prodrug sulindac reduces the growth of existing polyps in familial adenomatous polyposis (FAP). However, the dose, duration of effect and length of protection seen after cessation remain to be fully established. Furthermore, in view of previous discrepancies between the results of observational studies and randomized control trials (RCTs), it is crucially important to investigate the effects of aspirin by RCTs. RCTs investigating the effect of chemopreventive agents on adenoma recurrence as an intermediate endpoint for colorectal cancer is a more feasible approach than RCTs to investigate the effect on the incidence if colorectal cancer per se. Four RCTs of the effect of aspirin on adenoma recurrence are available. Other trials are currently underway.

Adenoma↗

Is colorectal cancer an avoidable disease nowadays?

Colorectal cancer is a major cause of cancer death in Western countries. Colorectal cancer screening is effective. To promote primary prevention and screening in high, increased as well as average risk populations remains a public health challenge. Chemoprevention of colorectal cancer that involves the long-term use of pharmacological agents as aspirin also seems to be effective.

Adenomatous Polyposis Coli↗

Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial.

BACKGROUND & AIMS: Epidemiologic and experimental studies have suggested that aspirin intake reduces the risk for colorectal carcinogenesis. However, the available data are not sufficient to serve as the basis for firm recommendations. METHODS: We randomly assigned 272 patients with a history of colorectal adenomas (at least one more than 5 mm in diameter, or more than 3) to daily lysine acetylsalicylate (160 or 300 mg/day) or placebo for 4 years. The primary end points were adenoma recurrence after 1 and 4 years. These results are those of the year 1 colonoscopy. RESULTS: Among the 238 patients who completed the year 1 colonoscopy, at least one adenoma was observed in 38 patients of the 126 (30%) in the aspirin group and in 46 of the 112 (41%) in the placebo group; relative risk was 0.73 (95% confidence interval [CI]: 0.52-1.04; P = 0.08). At least one adenoma of more than 5 mm diameter was observed in 13 patients (10%) in the aspirin group and 26 (23%) in the placebo group (P = 0.01). The corresponding numbers for adenomas more than 10 mm in diameter were one (1%) and 7 (6%) (P = 0.05). Stepwise regression showed that independent factors associated with lower adenoma recurrence are aspirin treatment (adenoma >5 mm, P = 0.01), absence of personal history of adenoma before the entry colonoscopy (P = 0.01), and initial adenomatous polyp burden less than 10 mm (P = 0.001). CONCLUSIONS: Daily soluble aspirin is associated with a reduction in the risk for recurrent adenomas found at colonoscopy 1 year after starting treatment.

Adenoma↗

Postprandial kinetics of dietary amino acids are the main determinant of their metabolism after soy or milk protein ingestion in humans.

Soy proteins have been shown to result in lower postprandial nitrogen retention than milk proteins, but the mechanisms underlying these differences have not been elucidated. To investigate this question, we measured the postprandial kinetics of the appearance of individual (15)N-amino acids in the serum of healthy adults after the ingestion of either (15)N-soy (n = 8) or (15)N-milk proteins (n = 8) in a mixed single meal (46 kJ/kg). The kinetics of total and dietary amino acids (AA) in the peripheral circulation were characterized by an earlier and higher peak after soy protein ingestion. Dietary AA levels peaked at 2.5 h in the soy group vs. 3.9 h in the milk group (P < 0.02). This time interval difference between groups was associated with a faster transfer of dietary N into urea in the soy group (peak at 3 vs. 4.75 h in the milk group, P < 0.005) and a higher level of incorporation into the serum protein pool from 3 to 8 h after the soy meal. The dietary AA pattern in the peripheral blood closely reflected the dietary protein AA pattern. Postprandial glucose, insulin, and glucagon levels and profiles did not differ between groups. Soy AA were digested more rapidly and were directed toward both deamination pathways and liver protein synthesis more than milk AA. We conclude that differences in the metabolic postprandial fates of soy and milk proteins are due mainly to differences in digestion kinetics; however, the AA composition of dietary proteins may also play a role.

Adult↗

Increasing habitual protein intake accentuates differences in postprandial dietary nitrogen utilization between protein sources in humans.

It is appropriate to characterize the nutritional value of dietary proteins in humans through the specific study of dietary nitrogen metabolism during the postprandial period. However, the influence of the habitual protein intake on this variable has not been studied. We aimed to describe the influence of prior protein intake on the specific metabolic utilization of dietary nitrogen in humans. Healthy men and women were adapted for 7 d to two diets with a normal [NP, 1 g/(kg x d)] and high protein content [HP, 2 g/(kg x d)]. After each period, they were studied for an 8-h postmeal period after ingesting a single (15)N-labeled mixed meal (0.41 g/kg protein) containing either milk (n = 12) or soy protein (n = 8). The HP diet reduced the peak of dietary N incorporation into free serum amino acids in the soy group but had no effect in the milk group. The incorporation of dietary N into plasma protein was higher after soy than after milk protein, but habitual protein level had no effect. The postprandial retention of milk protein was reduced by the HP diet compared with the NP diet by only 5% and that of soy protein was diminished by 13% (protein source: P < 0.0001, protein level: P < 0.0001, interaction: P < 0.001). In conclusion, the efficiency of the meal N postprandial retention was lower after HP adaptation, but this decrease was much more pronounced for soy than for milk protein, indicating that increasing the habitual protein intake accentuates differences in metabolic utilization among dietary proteins.

Adult↗

Ileal losses of nitrogen and amino acids in humans and their importance to the assessment of amino acid requirements.

BACKGROUND & AIMS: Irreversible amino acid losses at the human ileum are not taken into account when tracer-derived amino acid requirements are calculated because the data available are scarce. We have investigated amino acid losses at the ileal level in humans after ingestion of a protein meal. METHODS: Thirteen volunteers ingested a single meal of 15N milk or soy proteins. The appearance of 15N and 15N amino acids in the ileal effluents collected using an ileal tube was monitored for 8 hours. RESULTS: In the soy group, higher losses of endogenous nitrogen, especially originating from amino acids, were observed, as well as a higher flow rate of dietary non-amino acid nitrogen. With soy protein, the digestibilities of valine, threonine, histidine, tyrosine, alanine, and proline were significantly lower than with milk. Ileal losses of leucine, valine, and isoleucine amounted to 12, 10, and 7 mg x kg(-1) x day(-1), respectively. Threonine ileal loss (9-12 mg x kg(-1) x day(-1)) was particularly high compared with the current amino acid requirement. CONCLUSIONS: Amino acid losses at the human terminal ileum are substantial and depend on the type of dietary protein ingested. Although it remains unclear whether intact amino acids are absorbed in the colon, we suggest that ileal losses should be considered an important component of amino acid requirements.

Adult↗

[Inappropriateness of hospital days and causes of failure in a Gastroenterology and Internal Medicine ward].

OBJECTIVES: To analyse patients' features linked to hospital inappropriateness and to highlight causes of inappropriate days in a Gastroenterology and Internal Medicine ward of a teaching hospital. METHODS: Appropriateness of patients' hospital days (2 months activity) was assessed using the French version of criteria of the Appropriateness Evaluation Protocol. Reasons of inappropriate hospital days were identified through a questionnaire based on patients' need. RESULTS: Two hundred and twenty patients were studied. Among the 2151 hospital days assessed, 880 (41%) were inappropriate. Two different groups of inappropriate stays were brought up. In the first group, the inappropriate period duration was short (<=5 days) and patients were not different from those of the appropriate group. In the second group, the inappropriate period duration was long ( > 5 days) and 710 days (33%) were inappropriate. Patients were elderly, lived alone and their disease did not concern the gastrointestinal tract. During inappropriate days, they expected access to less technical facilities than the short stay medical ward. CONCLUSION: The socio-demographic and medical features of the patients from the long duration inappropriateness group should help to limit inappropriate hospital days: a significant economic and organizational stake for patients, hospital and public interest.

Adult↗