Developing a strawberry yogurt fortified with marine fish oil.

Fortified dairy products appeal to a wide variety of consumers and have the potential to increase sales in the yogurt industry and help increase intake of long-chain n-3 fatty acids. The objectives of this study were to develop a strawberry yogurt containing microencapsulated salmon oil (MSO; 2% wt/vol) and evaluate its characteristics during 1 mo of storage. Unpurified salmon oil (USO) was purified (PSO) and both USO and PSO were analyzed for peroxide value (PV), anisidine value (AV), total oxidation, free fatty acids (FFA), and moisture content. A stable emulsion was prepared with 7% PSO, 22% gum arabic, 11% maltodextrin, and 60% water. The emulsion was spray-dried to produce MSO. The MSO was added to strawberry-flavored yogurt (SYMSO) before pasteurization and homogenization, and a control (SY) without MSO was produced. Both yogurts were stored for 1 mo at 4°C and we determined the quality characteristics including acidity (pH), syneresis, thiobarbituric acid (TBA), fatty acid methyl ester composition, color, and lactic acid bacteria (LAB) count. The entire experiment was replicated 3 times. Total oxidation (unitless) of USO, PSO, and MSO was calculated to be 20.7±1.26, 10.9±0.1, and 13.4±0.25, respectively. Free fatty acid contents were 1.61±0.19%, 0.59±0.02%, and 0.77±0.02% for USO, PSO, and MSO, respectively. Eicosapentaenoic acid and docosahexaenoic acid were the predominant polyunsaturated fatty acids in MSO and in SYMSO, but neither was detected in SY. Fortification of SY with MSO had no significant effect on yogurt pH or syneresis. A decrease in concentration of lactic acid bacteria was observed during the storage of all yogurts. Thiobarbituric acid values significantly increased as storage time increased and SY had a significantly lighter (higher L*) and less yellow (lower b*) color than SYMSO. Although some slight differences were observed in the color and oxidation of SYMSO compared with SY, the study demonstrated that SY could be fortified with salmon oil.

Gelation, oxygen permeability, and mechanical properties of mammalian and fish gelatin films.

The objective of this study was to evaluate the gelation, thermal, mechanical, and oxygen permeability properties of different mammalian, warm- and cold-water fish gelatin solutions and films. Mammalian gelatin solutions had the highest gel set temperatures, followed by warm-water fish and then cold-water fish gelatin solutions. These differences were related to concentrations of imino acids present in each gelatin, with mammalian gelatin having the highest and cold-water fish gelatin having the lowest concentrations. Mammalian and warm-water fish gelatin films contained helical structures, whereas cold-water fish gelatin films were amorphous. This was due to the films being dried at room temperature (23 °C), which was below or near the gelation temperatures of mammalian and warm-water fish gelatin solutions and well above the gelation temperature of cold-water fish gelatin solutions. Tensile strength, percent elongation, and puncture deformation were highest in mammalian gelatin films, followed by warm-water fish gelatin film and then by cold-water fish gelatin films. Oxygen permeability values of cold-water fish gelatin films were significantly lower than those for mammalian gelatin films. These differences were most likely due to higher moisture sorption in mammalian gelatin films, leading to higher oxygen diffusivity.

Effect of salmon type and presence/absence of bone on color, sensory characteristics, and consumer acceptability of pureed and chunked infant food products.

Salmon-based infant food (puree) and toddler food (puree plus chunks) were manufactured from pink salmon, with and without bone, and from Sockeye salmon, with and without bone, to contain 45% salmon, 55% water, and 5% starch. Products were retort processed at 118 to 121 degrees C for 55 min in a steam-jacketed still retort. A trained descriptive panel (n = 7) evaluated infant and toddler foods separately. Instrumental color, pH, and water activity were also determined. Infant and toddler foods were also evaluated by a consumer panel (n = 104) of parents for product acceptability. During the manufacturing process (cooking, homogenization, retort processing), salmon infant food from pink salmon lost much of its characteristic pink color while that from sockeye salmon retained a greater amount. Bitterness was more evident in samples with bones. In the toddler food formulation containing chunks, the odor and flavor characteristics were influenced primarily by the type of salmon. The presence of bone affected visual pink color and lightness, and salmon odor only. Consumers scored products made with sockeye salmon as more acceptable despite the fact that they had more off-flavor than products from pink salmon. The appearance and thickness of the pureed infant food was more acceptable than the toddler food with chunks despite the chunky toddler product having more acceptable salmon flavor. This indicates that the color and appearance of the prototypes were the main drivers for liking. Of the total number of parents surveyed, 73% would feed this salmon product to their children.

Effect of inclusion of salmon roe on characteristics of salmon baby food products.

Baby food was formulated from sockeye salmon (puree alone, puree + chunks, puree + pink row, puree + pink row + chunks, puree + red row, puree + red roe + chunks). In the 1st study, physical (pH, instrumental color, water activity) and descriptive sensory (odor, flavor, texture, visual color) characteristics were determined. Samples containing roe were lighter and less red (by approximately 3 to 4 a* units) than formulations without roe regardless of the type of roe added. Visual pink color followed the same trend. Formulations with roe, both pink and sockeye, were almost twice as fibrous as formulations without roe. Salmon flavor was stronger in samples containing roe from sockeye salmon. In the 2nd study, retort processed samples were stored at room temperature for 6 mo. Sweaty odor decreased over storage time. Visual cream-brown color correlated with L*, a*, b*, and chroma values (r =-0.80, 0.75, 0.80, and 0.84, respectively). TBARS values of all samples were < 0.35 mg MDA/kg and declined after month 0 indicating that these products were oxidatively stable. Overall, adding roe to these products lightened them and increased fibrous texture. Samples containing sockeye salmon roe had stronger salmon flavor. Once retort processed, these products were quite stable in terms of color, odor, and TBARS. Potential nutrient contributions of this type of product to the infant diet warrant additional research.

Protein digestibility evaluations of meat and fish substrates using laboratory, avian, and ileally cannulated dog assays.

Meat and fish serve as important protein sources in the companion animal diet; however, limited protein digestibility data are available for assessing protein digestibility differences among good-quality protein sources. Beef loin, pork loin, chicken breast, pollock fillet, and salmon fillet were evaluated for composition, protein digestibility, and AA bioavailability using the immobilized digestive enzyme assay, cecectomized rooster assay, and ileally cannulated dog assay. Pollock contained the greatest amount of CP, total essential AA (TEAA), and total nonessential AA (TNEAA; DM basis; 96.9, 38.6, and 50.3%, respectively). Salmon contained the next greatest amounts (92.8, 36.4, and 44.6%), followed by chicken (90.3, 36.1, 43.2%). Beef had the least CP content (82.7%), but had slightly greater TEAA and TNEAA concentrations (33.9, 42.0%) compared with pork (86.2, 33.6, 41.3%). Immobilized digestive enzyme assay values were greatest for pollock fillet (0.71) and least for chicken breast (0.52). Beef loin, pork loin, and salmon fillet were similar (0.63, 0.62, and 0.64, respectively). Standardized TEAA and TNEAA digestibility coefficients, evaluated using the cecectomized rooster assay, were greatest (P < 0.05) for pollock fillet (90.4 and 89.8%, respectively) and least (P < 0.05) for chicken breast (86.6 and 85.9%, respectively) and salmon fillet (87.8 and 86.4%, respectively). Dogs assigned to a 5 x 5 Latin square design were fed 5 diets, with each test substrate as the major protein source. No significant differences (P > 0.05) were found in ileal digestibility of protein. Values ranged from 88.9% for chicken to 90.5% for pork loin and pollock fillet. Ileal TEAA and TNEAA coefficients were not different among test substrates, with values between 91.7 and 92.7%, and 88.8 and 90.4%, respectively. Total tract CP apparent digestibility values ranged from 94.4 to 94.8%, with no differences noted among treatments. Despite marked differences in composition and predicted and standardized digestibility values, when the protein sources were added to diets at a concentration of approximately 30% (25% of total energy intake), no differences in test protein substrates were noted in either ileal or total tract nutrient digestibility.

Fish protein substrates can substitute effectively for poultry by-product meal when incorporated in high-quality senior dog diets.

An experiment was conducted to analytically define several novel fish substrates and determine the effects of feeding diets containing these substrates on total tract nutrient digestibilities and on immune status of senior dogs. The control diet contained poultry by-product meal while test diets contained 20% milt meal (MM), pink salmon hydrolysate (PSH) and white fish meal (WFM) added at the expense of poultry by-product meal. Concentrations of lymphocytes positive for CD3, CD4, CD8 and CD21 cell-surface markers and immunoglobulin concentrations were measured. Gene expression of cytokines tumour necrosis factor (TNF)-, interleukin (IL)-6, interferon (IFN)-, IL-10 and transforming growth factor (TGF)-ß was determined by quantitative real-time polymerase chain reaction. Major compositional differences were noted among fish substrates but apparent nutrient digestibility coefficients and immune indices were not affected by treatment. Fish protein substrates were found to be effective substitutes for poultry by-product meal, providing diets of high nutritive value for senior dogs.

Carcass composition and yield of Alaskan reindeer (Rangifer tarandus tarandus) steers and effects of electrical stimulation applied during field slaughter on meat quality.

Twenty six adult reindeer steers (>3 years old) were used in a study to evaluate the effect of electrical stimulation (ES) on the quality of hot-boned, rapidly frozen shoulder meat and of the striploin (M. longissimus, LD) from carcasses held at +3°C for 48h. Carcass yield and composition was determined from the left carcass half from which the shoulder meat was not removed. The shoulder meat was processed frozen into cubed, sliced or ground products. Proximate composition of the LD, meat color and water-holding capacity were very similar for the ES (n=15) and non-electrical stimulation (NES; n=11) groups. Ultimate pH and shear force values were significantly lower in the ES meat (LD), however a trained sensory panel could not detect differences between the two groups in any of the measured sensory attributes. Consumer preference tests demonstrated that ES increased tenderness in the cubed and sliced products made from field slaughtered reindeer shoulder meat. ES in combination with hot boning and processing of boneless frozen meat can be used in field slaughter systems for reindeer to improve meat quality and to increase the potential value of the carcass.

Characterization of protein fractions from immature Alaska walleye pollock (Theragra chalcogramma) roe.

There are good markets for mature pollock roe; however, immature pollock roe is underutilized. The physical and nutritional properties of immature pollock roe (IPR) have not been reported, which limits its potential use as a food ingredient. The objective of this study was to evaluate the physical and nutritional properties of immature pollock roe and soluble and insoluble protein powders made from the immature roe. IPR samples were obtained during the spring pollock harvest from a seafood processing plant in Kodiak, Alaska. Soluble (SP) and insoluble protein (IP) fractions were produced by heating IPR, separating by centrifugation and freeze drying. The protein contents of freeze-dried IPR, SP, and IP were 81.7%, 63.2%, and 83.0%, respectively. The amino acid contents of IPR and IP were similar except for isoleucine and valine. However, the amino acid contents of IPR and IP were different from values for SP. Lipid contents of IPR, SP, and IP were 9.2%, 9.3%, and 11.1%, respectively. Palmitic acid (C16:0; 21.2%), DHA (C22:6omega3; 21.2%), and EPA (C20:5omega3; 19.0%) were the 3 most abundant fatty acids in fresh IPR. Fat adsorption capacity value for SP was significantly higher than IPR and IP (P < 0.05). SDS electrophoresis indicated a major protein band with molecular weight of 103 KDa in all samples. Results indicate that IPR can be utilized to make a number of unique food ingredients with good nutritional characteristics and functional properties.

Fish meals, fish components, and fish protein hydrolysates as potential ingredients in pet foods.

An experiment to determine the chemical composition and protein quality of 13 fish substrates (pollock by-products, n = 5; fish protein hydrolysates, n = 5; and fish meals, n = 3) was conducted. Two of these substrates, salmon protein hydrolysate (SPH) and salmon meal with crushed bones (SMB), were used to determine their palatability as components of dog diets. Pollock by-products differed in concentrations of CP, crude fat, and total AA by 71, 79, and 71%, respectively, and GE by 4.1 kcal/g. Fish protein hydrolysates and fish meals were less variable (approximately 18, 14, and 17%, and 1.4 kcal/g, respectively). Biogenic amine concentrations were much higher in fish protein hydrolysates as compared with pollock by-products and fish meals. Pollock liver and viscera had the highest total fatty acid concentrations; however, red salmon hydrolysate and SMB had the highest total PUFA concentrations (49.63 and 48.60 mg/g, respectively). Salmon protein hydrolysate had the highest protein solubility in 0.2% KOH. Based on calculations using immobilized digestive enzyme assay values, lysine digestibility of fish meal substrates was comparable to in vivo cecectomized rooster assay values and averaged approximately 90.3%. Also, pollock milt, pollock viscera, red salmon hydrolysate, and sole hydrolysate had comparable values as assessed by immobilized digestive enzyme assay and rooster assays. A chick protein efficiency ratio (PER) assay compared SMB and SPH to a whole egg meal control and showed that SMB had high protein quality (PER = 3.5), whereas SPH had poor protein quality (PER value less than 1.5). However, using whole egg meal as the reference protein, both fish substrates were found to be good protein sources with an essential AA index of 1.0 and 0.9 for SMB and SPH, respectively. In the dog palatability experiments, a chicken-based control diet and 2 diets containing 10% of either SPH or SMB were tested. Dogs consumed more of the SPH diet compared with the control, and similar amounts of the SMB and control diets. The intake ratios for each were 0.73 and 0.52, respectively. Salmon protein hydrolysate was especially palatable to dogs. These data suggest that chemical composition and nutritional quality of fish substrates differ greatly and are affected by the specific part of the fish used to prepare fish meals and fish protein hydrolysates.

[Clinical relevance of N-acetyltransferase type 2 (NAT2) genetic polymorphism]. / Pertinence clinique du polymorphisme génétique de la N-acétyltransférase de type 2 (NAT2).

Polymorphic N-acetyltransferase (NAT2) is involved in the metabolism of several compounds relevant in pharmacology or toxicology, with diverse clinical consequences. Inter-ethnic variations in distribution of the acetylation phenotype are significant. The caffeine test is most often used to assess the acetylation phenotype and to identify rapid and slow acetylators. The NAT2 phenotype could account for the increased risk of certain side effects in slow acetylators treated with isoniazid (particularly peripheral neuropathies and lupus erythematosus), although therapeutic efficacy seems to be independent of the acetylation status. Hypersensibility reactions with sulfonamides (including Lyell and Stevens-Johnson syndromes) are more frequent in slow acetylators, who also show poor tolerance to sulfasalazine and dapsone. In contrast, myelotoxicity induced by amonafide is more frequent in rapid acetylators, probably because of increased production of a toxic metabolite of the drug. In carcinogenesis, NAT2 may play a protective role against bladder cancer, although studies have shown contradictory results. Slow acetylators may have a risk of developing primitive liver cancer. For lung cancer, data are not conclusive, but slow acetylation status may predispose to mesothelioma in subjects exposed to asbestos. No relation has been found between acetylation phenotype and breast cancer. Contradictory results were reported on its role in colorectal cancer. Non-smoking type 1 diabetics may be at increased risk of nephropathy if they are rapid acetylators. Parkinson's disease may be more frequent among slow acetylators, but again, data have shown contradictory results. Finally, a poor acetylator phenotype may predispose to atopic diseases.

[The acetylator polymorphism in a Khmer population: clinical consequences]. / Polymorphisme d'acétylation dans une population khmère: conséquences cliniques.

The great variability of slow acetylator (SA) and/or rapid acetylator (RA) frequency is mainly due to ethnic-racial origin. Using the urinary elimination ratio of three metabolites of caffeine--acetylamino formylamino methyluracil (AFMU) to AFMU + 1-methyl urate (1U) + 1-methyl xanthine (1X)--we settled the acetylation phenotype in 54 independent subjects of Khmer and 70 independent subjects of Caucasian origin. Using DNA from peripheral leucocytes, we determined by PCR, in 32 Khmer and 122 Caucasian subjects, the frequencies of wild-type alleles (NAT-2 *4) and of mutated alleles (NAT-2 *5A, *6A, *7A). The frequency of SA was respectively 28 per cent and 61 per cent in Khmer and Caucasian subjects. The antimode of the distribution of the ratio was different in the two populations: 0.07 in Khmers and 0.18 in Caucasians showing a reduced acetylation capacity in the Khmer population in spite of a higher frequency of RA. The frequencies of alleles were also different between the two populations. Between Khmers and Caucasians respectively: *4: 48.4-23.8 per cent *5A: 15.6-44.2 per cent. *6A: 29.7-32.0 per cent. *7A: 6.3-0 per cent. These differences might be taken into account to define a therapeutic strategy in the treatment of tuberculosis by isoniazide.

Caffeine metabolism before and after liver transplantation.

AIM: To study drug metabolism in patients before and after liver transplantation using caffeine as a probe drug. Forty-five patients undergoing liver transplantation for various liver diseases and who had well documented dossiers were selected for the study. Before the liver transplantation and 1 month, 1 year, and 6 years after liver transplantation, they were given 200 mg of caffeine by the oral route in the morning after voiding their bladder. Twenty-four-hour urine samples were collected and caffeine and metabolites were determined by HPLC: 1-methylurate (1U), 1-methylxanthine (1X), 1.7-dimethylurate (17U), 1.7-dimethylxanthine (17X), 7-methylxanthine (7X), 3-methylxanthine (3X), 1.3-dimethylurate (13U), 3.7-dimethylxanthine (37X), 1.3-dimethylxanthine (13X), 1.3.7-trimethylxanthine = caffeine (137X). Indices of enzyme activities were calculated from the following urinary elimination ratios: (AFMU+1U+1X)/17U for CYP1A2, 17U/17X for CYP2A6, 1U/1X for xanthine oxidase (XO), AFMU/(AFMU+1U+1X) for N-acetyltransferase (NAT-2). RESULTS: Compared with results obtained in a group of 70 healthy subjects, caffeine metabolism before liver transplantation was deeply depressed with a decreased elimination rate in the case of all metabolites and a decreased CYP1A2 activity. Caffeine metabolism began to return to the control values one month after transplantation. One year and 6 years after liver transplantation, quantitatively, the metabolism of caffeine was stable and not different from control, but with qualitative modifications. CYP1A2 activity was decreased with reduced urinary elimination rates of 1X and 17X. XO and CYP2A6 activities and 1U and 17U urinary elimination rates were increased. Immunosuppressive treatment was possibly responsible for the metabolic pathway changes. Almost the same modifications were observed in 9 patients after bone marrow transplantation who had been treated with the same immunosuppressive drugs, cyclosporine and azathioprine. During severe rejection phases in 6 of the liver transplant patients, caffeine metabolism was progressively decreased when the usual liver function tests showed moderate but uniform changes. CONCLUSION: Despite an apparent normal drug-metabolic function, immunosuppressive treatment induces stable variations in drugmetabolic pathways after liver transplantation which can be detected from the changes in caffeine metabolism.

Caffeine metabolism in a group of 67 patients with primary biliary cirrhosis.

OBJECTIVE: To evaluate the polygenic regulated caffeine metabolism in a group of 67 patients with a documented primary biliary cirrhosis (PBC) classified according to the histologic stage proposed by Scheuer. METHODS: Over a 14-year period, drug liver metabolism, using caffeine as a probe drug, has been systematically carried out in addition to the usual clinical, histological and biochemical investigations performed in patients with PBC. The "Caffeine test" consisted of a 200 mg caffeine oral intake. Urines were collected over 24 hours: caffeine (137X), 1-7-dimethylxanthine (17X), 1-3-dimethylxanthine (13X), 1-3-dimethylurate (13U), 3-7-dimethylxanthine (37X), 1-7-dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), 7-methylxanthine (7X), 3-methylxanthine (3X), and 5-acetylamino-6-formylamino-3-methyluracyl (AFMU) were analyzed by high performance liquid chromatography (HPLC). Total and individual metabolite urinary elimination rates were expressed in micromol/24 hours. Enzyme activities were evaluated from the following urinary metabolite ratios: (AFMU+1U+1X)/17U for CYP1A2, 17U/17X for CYP2A6, AFMU/(AFMU+U+ 1X) for NAT-2, 1U/1X for XO. RESULTS: Compared to healthy subjects, patients with PBC presented a reduced metabolism of caffeine due to a decreased CYP1A2 activity, all the more important since the patients had an advanced histological stage. This picture was nearly identical to the observed picture in chronic liver diseases from various origins. PBC affected the various metabolic pathways of caffeine in a differential manner. CYP1A2 activity was decreased but XO and mainly CYP2A6 activities were increased as shown by the raised urinary ratio 17U/total metabolite elimination. In contrast to the described loss of bimodality of the NAT-2 index distribution in patients with alcoholic cirrhosis, we found a clear-cut, bimodal distribution in patients with PBC, without a high incidence of slow acetylator status. CONCLUSION: Metabolism of caffeine is strongly and differentially disturbed in patients with PBC and apparently not exactly in the same way as that in alcoholic cirrhosis which is more often taken as an index of chronic liver disease. This suggests the need for caution with medicines whose metabolism is under polygenic regulation. Because of the relationships between caffeine metabolism modifications and histological stages, the caffeine test might be used along with the usual tests to safely follow-up the evolution of the disease.

Population pharmacokinetics of clomipramine, desmethylclomipramine, and hydroxylated metabolites in patients with depression receiving chronic treatment: model evaluation.

Because metabolites play a major role in the clinical response to clomipramine, the objective of the current study was to develop a population model and evaluate its performance to describe the pharmacokinetic profiles of clomipramine (C) and its active metabolites desmethylclomipramine (DC), 8-hydroxy-clomipramine (OHC) and 8-hydroxy-desmethylclomipramine (OHDC). A first sample of 14 patients served for development of a 2-molecule C and DC model, which was shown to provide reasonable estimates of AUC-based clearances, as well as precise estimation of interindividual variability. Simulated data, generated to mimic a semi-rich sampling design and chronic treatment with clomipramine, indicated that clearance estimation was feasible under routine treatment conditions. A second sample of 30 patients, recruited prospectively and followed for a median 4-week period, was used to extend the 2-molecule model to a 4-molecule model. Goodness-of-fit assessment revealed that model-predicted concentrations were reasonably close to observed concentrations for a majority of patients. Interindividual variability was 50% to 60% for hydroxylation and desmethylation clearances, and residual variability was 30%. The proposed model incorporates much of what is known about the metabolism of clomipramine and may valuably integrate the influence of genetic and environmental factors on each metabolic pathway.

Relationship between the severity of alcoholic liver cirrhosis and the metabolism of caffeine in 226 patients.

OBJECTIVES: To evaluate the polygenic regulated caffeine metabolism in a group of 226 patients with liver alcoholic cirrhosis classified according to the Child score. METHODS: Over a 14-year period an hepatic function test, using caffeine as probe drug, has been systematically associated to the usual clinical and biochemical investigations performed in patients with liver alcoholic cirrhosis. "Caffeine test" consisted in a 200 mg caffeine oral intake. Urines were collected over 24 hours: caffeine (137X), 1-7 dimethylxanthine (17X), 1-3 dimethylxanthine (13X), 1-3 dimethylurate (13U), 3-7 dimethylxanthine (37X), 1-7 dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), 7-methylxanthine (7X), 3-methylxanthine (3X), and 5-acetylamino-6-formylamino-3-methyluracyl (AFMU) were analyzed by high performance liquid chromatography (HPLC). Total and individual metabolite urinary elimination rates were expressed in micromol/24 hours. Enzyme activities were evaluated from the following urinary metabolites ratios: (AFMU+1U+1X)/17U for CYPIA2, 17U/17X for CYP2A6, AFMU/(AFMU+ 1U+1X) for NAT-2, 1U/1X for XO. RESULTS: Compared to healthy subjects, whatever the Child score, caffeine metabolism was reduced by half in patients with alcoholic cirrhosis. The main cause was the decreased CYP1A2 activity. On the other hand, XO and CYP2A6 activities were increased and NAT-2 activity remained unchanged in slow acetylators (SA) and decreased in rapid acetylators (RA) Child B and C. Bimodality of NAT-2 distribution was unclear, but a right assignment of RA and SA phenotype in cirrhotic patients, confirmed by comparison with genotype, was obtained, using the antimode value of NAT-2 distribution used in healthy subjects. At last, there was an interindividual variability in caffeine metabolism as great as in the usual laboratory parameters. CONCLUSION: Metabolism of caffeine is decreased in patients with alcoholic liver cirrhosis. This decrease paralleled the modifications of the usual laboratory tests and does not bring additional information on the severity of the disease. But the equilibrium between the various metabolic pathways of caffeine is impaired. Beyond the changes of a specific enzymatic activity, this must be taken into account particularly for drugs whose metabolism is of the polygenic regulation type.

Similarities and/or dissimilarities of CYP2D6 polymorphism in three Tunisian ethnic groups: Arabs, Berbers, Numides.

Using the validated probe drug debrisoquine and the 8 h urinary metabolic ratio debrisoquine/4 hydroxy-debrisoquine, we have determined the phenotype of the debrisoquine CYP2D6 dependent polymorphic metabolism in 464 Arabs, 227 Berbers and 215 Numides to elicit similarities or dissimilarities of poor metabolizer (PM) prevalence. We found 2.36 per cent of PM in Arabs, 3.08 per cent in Berbers and 2.33 per cent in Numides. These figures are similar to those observed in Middle East populations, and cannot be considered as different from those observed in Caucasians.

Analysis of N-acetyltransferase (NAT2) in three ethnic groups in Tunisia.

Acetylation status was compared, using caffeine as a probe drug, in the three main racial/ethnic groups living in Tunisia: Arabs, Berbers and Numides. The frequency of slow acetylators appears identical in these three groups and is different from that observed in Caucasians. However, the NAT-2 activity as a whole is lower in Tunisians than in Caucasians. These differences might be attributable to the various population mixings which occurred in the past, given the geographical position of Tunisia. It may be asked whether these differences are relevant in term of efficiency and/or frequency of adverse drug reactions when medicines whose metabolism is NAT-2 dependent are used. This hypothesis deserves to be tested.

On the assessment of drug metabolism by assays of codeine and its main metabolites.

Codeine and its main metabolites appear to have advantages for assessing drug metabolic phenotypes. The authors have further developed a high-performance liquid chromatography (HPLC) method for the quantification of codeine and six of its metabolites in urine. Quantification was performed by electrochemical detection for morphine, normorphine, morphine-6-glucuronide, and the internal standard 4-O-methyldopamine; and by ultraviolet detection for codeine, norcodeine, and morphine-3-glucuronide. The method had a detection limit of 2 nmol/L(-1) for morphine and normorphine, 4 nmol/L(-1) for morphine-6-glucuronide, 3 nmol/L for the internal standard, 20 nmol/L(-1) for morphine-3-glucuronide, and 60 nmol/L(-1) for codeine and norcodeine. The coefficients of variations were <9% for intraday and <10% for interday analyses. The recovery of codeine and its metabolites ranged from 55% (for morphine-3-glucuronide) to 90% (for codeine, norcodeine, morphine, and morphine-6-glucuronide). Eleven healthy volunteers were phenotyped for CYP2D6 using codeine as well as debrisoquine and dextromethorphan. Ten subjects were extensive metabolizers (EM) and one a poor metabolizer (PM) of codeine, debrisoquine, and dextromethorphan. Significant correlations between the metabolic ratios (MRs) of the different probe drugs were obtained (r2 > 0.95, p < 0.001). This HPLC method is simple, sensitive, accurate, and reproducible for assessing the CYP2D6 phenotype.

Caffeine metabolism differences in acute hepatitis of viral and drug origin.

The 24-h urinary excretion rate of caffeine metabolites following 200 mg caffeine intake has been proved to be a valuable safe quantitative test of liver function. The pathological mechanism of acute hepatitis of viral and drug origin is different. In both diseases, the patient's caffeine metabolic capacity during the acute and the recovery period was compared. In the acute period, in both diseases, the strongly reduced metabolism of caffeine paralleled the variations of the usual biochemical tests. During the recovery period, in viral hepatitis, caffeine metabolism and biochemical tests returned to the normal values. In drug-induced hepatitis during the recovery period, caffeine metabolism remained severely impaired at a time when biochemical tests were back to the control levels. This discrepancy might be due to the histological or molecular toxic effects of the drug(s), irrespective of cytolysis. After drug-induced hepatitis, a caffeine test might be used to check the total recovery or to choose an adapted dosage of medicines.