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1.
J Food Prot ; 64(9): 1405-11, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11563519

RESUMO

Beef patties (86 and 143 g) formed from high-fat (20 to 29%) and low-fat (6 to 10%) ground beef obtained in eight different selections for both high and low fat content were cooked by either a gas grill or an electric griddle. Patties were cooked to either 66.1 or 68.3 degrees C as determined in the thickest section, and internal temperatures were recorded after cooking at 1-s intervals for 180 s in both thick and thin sections of patties. Time-temperature curves (after cooking) were evaluated for compliance with regulatory requirements for classifying patties as fully cooked. For patties cooked to 66.1 degrees C, the maximum highest temperature in the thickest patty section often did not reach 71.1 degrees C (recommended for cooking of beef patties by consumers). Although thin sections of patties had higher temperatures than thick sections at the termination of cooking, temperature variability was greater and declines in temperature occurred sooner in thin patty sections. Failure to meet fully cooked, time-temperature requirements was greater in thin than thick sections. Thicker (143-g) patties possessed longer postcooking times before declining in temperature than thinner (86-g) patties. Although many beef patties cooked in this study achieved regulatory time requirements for maintaining 66.1 or 68.3 degrees C (as well as attaining 71.1 degrees C), some patties did not meet these requirements. Because of the considerable temperature variability that can exist within patties at the conclusion of cooking, use of end point temperatures of less than 71.1 degrees C is not recommended for consumers. Consumers should allow several minutes of holding following cooking before consumption to maximize the increases in postcooking temperature. Further research is required to establish cooking procedures that will improve temperature uniformity and eliminate "cold spots" during cooking of beef patties.


Assuntos
Culinária/métodos , Carne/microbiologia , Animais , Bovinos , Contagem de Colônia Microbiana , Cor , Qualidade de Produtos para o Consumidor , Culinária/instrumentação , Microbiologia de Alimentos , Temperatura Alta , Humanos , Controle de Qualidade
2.
J Food Prot ; 63(10): 1389-98, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11041139

RESUMO

An interlaboratory study was undertaken to assess the frequency that cooked color of ground beef patties appeared brown at internal temperatures of 52.7 degrees C (135 degrees F), 65.6 degrees C (150 degrees F), 71.1 degrees C (160 degrees F), and 79.4 degrees C (175 degrees F). In general, as internal cooked temperature of the patties increased, the following results were observed in the patties: (i) more brown meat color, (ii) less pink or red juice color, and (iii) more cooked texture. However, brown meat color occurred prematurely at the two lower internal temperatures (57.2 degrees C/135 degrees F and 65.6 degrees C/150 degrees F) that are insufficient to eliminate foodborne pathogens without holding times. The common consumer practice of freezing bulk ground beef, followed by overnight thawing in a refrigerator, led to substantial premature brown color in patties cooked from this product. In addition, at 71.1 degrees C (160 degrees F), recognized to be the lowest temperature for cooking ground beef safely in the home, meat color, juice color, and texture appearance were not fully apparent as doneness indicators. In fact, at no temperature studied did 100% of the patties appear done when evaluated by the criteria of no red or pink in the meat, no red or pink in the juices, or by texture appearance. Patties in this study were evaluated under a set protocol for forming the products, cooking, and viewing under the same lighting conditions. Other preparation conditions are possible and may produce different results. Thus, temperature to which patties have been cooked cannot be judged by color and appearance. This study provided the evidence to support the message to consumers regarding cooking of beef patties of "use an accurate food thermometer and cook beef patties to 160 degrees F (71.1 degrees C)" in place of messages based on consumer judgment of cooked color.


Assuntos
Cor , Qualidade de Produtos para o Consumidor/normas , Culinária/métodos , Manipulação de Alimentos/métodos , Temperatura Alta , Carne/normas , Animais , Bovinos , Manipulação de Alimentos/normas , Carne/microbiologia , Mioglobina/efeitos adversos , Oxirredução
3.
J Food Prot ; 62(2): 156-61, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10030635

RESUMO

The objectives were to (i) compare the use of triose phosphate isomerase (TPI) activity and internal color scores for determination of cooking adequacy of beef patties and (ii) determine the effect of frozen storage and fat content on residual TPI activity in ground beef. Ground beef patties (24.4% fat) were cooked to five temperatures ranging from 60.0 to 82.2 degrees C. TPI activity decreased as beef patty cooking temperature was increased from 60.0 to 71.1 degrees C; however, no difference (P > 0.05) in activity (6.3 U/kg meat) was observed in patties cooked to 71.1 degrees C and above. Degree of doneness color scores, a* values and b* values, of ground beef patties decreased as internal temperature was increased from 60.0 to 71.1 degrees C; however, temperature had no effect on L* values. TPI activity in raw ground beef after five freeze-thaw cycles did not differ from the control. Three freeze-thaw cycles of raw ground beef resulted in a 57.2% decrease in TPI activity after cooking. TPI activity of cooked beef increased during 2 months of frozen storage, but TPI activity in ground beef stored for 3 months or longer did not differ from the unfrozen control. While past research has shown color to be a poor indicator of adequate thermal processing, our results suggest that undercooked ground beef patties could be distinguished from those that had been adequately cooked following U.S. Department of Agriculture guidelines using residual TPI activity as a marker.


Assuntos
Culinária , Manipulação de Alimentos/normas , Produtos da Carne/microbiologia , Triose-Fosfato Isomerase/metabolismo , Animais , Bovinos , Cor , Colorimetria , Manipulação de Alimentos/métodos , Congelamento , Alimentos Congelados , Temperatura Alta , Lipídeos/análise , Produtos da Carne/análise , Produtos da Carne/normas , Indústria de Embalagem de Carne/normas
4.
Meat Sci ; 53(1): 37-43, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22062931

RESUMO

This study was conducted to further understand the role that hot processing and grind size exert on cooked beef patty tenderness and other properties. Low-fat (10%) hot-processed (HP) and cold-processed (CP) beef were ground either through a 0.32 or 0.40 cm plate. A 20% fat CP product was also manufactured through a 0.32 cm plate. HP patties had higher pH, shorter sarcomere lengths, higher tenderness scores (including greater number of smaller particles during chewing) lower shear force values, higher flavor scores, less well-done cooked color, longer cooking times and higher cooking yields than CP patties (p<0.01). The use of a 0.32 cm rather than a 0.40 cm plate improved tenderness properties, especially for HP patties. Other properties were not greatly influenced by grind size. Sensory evaluation and scanning imagery of patties suggested that the greater tenderness of hot processed patties may be due to the presence of smaller meat particles. Highly contracted muscle, providing resistance to grinding, could be responsible for the small meat particles.

5.
J Appl Microbiol ; 82(3): 359-64, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12455900

RESUMO

We report a quantitative PCR which utilizes primers from a conserved 23S rDNA sequence identified in nine different spoilage bacteria commonly present in meat. The PCR detected the spoilage bacteria by amplifying a specific 207 bp sequence from their chromosomal DNA. Quantification of PCR product by electrochemiluminescence revealed that the concentration of the amplified product was dependent on cycle number and the initial number of bacteria present in the sample. Statistical analysis of the results indicated a correlation coefficient of 0.94 (P < 0.001) between aerobic plate count and QPCR luminosity units.


Assuntos
Bactérias/isolamento & purificação , Carne/microbiologia , Reação em Cadeia da Polimerase/métodos , RNA Ribossômico 23S/genética , Microbiologia de Alimentos , Conservação de Alimentos , Medições Luminescentes , Indústria de Embalagem de Carne
6.
J Anim Sci ; 75(2): 571-7, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9051482

RESUMO

Chevon (goat meat) is a low-fat red meat and thus may be an excellent source of lean in the preparation of low-fat meat products. This paper examines some of the textural, nutrient, and sensory properties of chevon products prepared from whole or comminuted muscle. Chops (2.54 cm thick) from the leg were either broiled at 232 degrees C or microwaved at a power level of 900 W. Results indicated that broiled chevon chops were not significantly different (P > .05) from microwaved chops in dimensional change, cooking yield, and instrumental force need to shear but were darker in color and had a significantly lower fat content than microwaved chops. Chevon patties were prepared from shoulder cuts by either grinding or chopping and cooked by pan-frying, broiling, or baking. Shear values were significantly affected by the method of comminution; grinding yielded patties with lower shear values. Pan-frying produced the highest cooking yields and shear values but the lowest fat content and instrumental lightness color values compared to the other cooking methods. Ground meat patties with an initial fat content between 4.6 and 13.8% were made with chevon and beef. The pan-fried patties made with 60% or more chevon gave higher (P < .05) cooking yields. However, a higher chevon content also resulted in significantly darker patties with higher shear values. Both consumer and trained sensory panels found similar sensory properties in patties having less than 60% chevon and more than 40% beef.


Assuntos
Culinária/métodos , Dieta com Restrição de Gorduras/normas , Tecnologia de Alimentos/métodos , Carne/normas , Animais , Cabras , Estatística como Assunto
7.
Meat Sci ; 42(1): 111-23, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-22060306

RESUMO

Three studies were conducted to determine the effects of electrical stimulation, hot processing and carrageenan usage on sensory, shear force and cooking properties of low-fat (5, 10%) beef patties. The right or left sides of beef carcasses assigned to electrical stimulation (ES) received 600 V pulsating current for 120 s. Non-stimulated (NS) sides were also included for comparisons. Sides subjected to hot processing (HP) were boned 90 min post-exsanguination. Cold processing (CP) was initiated 48 h post mortem. Formulations for the manufacture of patties included the use of carrageenan [none, 0.5% iota (ι), 0.5% kappa (κ)]. Patties from NSHP beef had higher pH and cooking yields, less shrink in patty dimensions during cooking and lower shear force values than patties from NSCP controls (P < 0.05). ES improved tenderness and juiciness of CP patties, while ESHP patties exhibited higher cooking yields than NSCP patties. Tenderness was improved in two of the three studies as a result of increasing the fat content from 5 to 10%. Use of ι-carrageenan provided improvements in tenderness and juiciness over patties receiving no carrageenan or κ-carrageenan. Processors should consider HP with 1.0% added salt (improved cooking yields, patty configuration, tenderness) and the use of ι-carrageenan (improved tenderness and juiciness) for low-fat beef patties.

8.
J Food Prot ; 59(8): 845-848, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31159124

RESUMO

The growth of spoilage bacteria results in a shorter shelf life of meat, causing economic losses to the meat industry. Based on 23S rDNA sequence data of Pseudomonas aeruginosa , two primers designated as PF (23 bases) and PR (20 bases) were synthesized for use in the polymerase chain reaction. A unique 207-base-pair DNA product from nine different bacteria typically associated with meat spoilage was amplified by the primers. Dot blot analysis with the internal DNA probe specific for the amplified products confirmed that the amplified DNA sequence is specific for the spoilage bacteria studied.

9.
Nucl Med Commun ; 16(4): 253-7, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7624105

RESUMO

Multi-drug resistance mediated by the transmembrane pump P-glycoprotein (Pgp) is an important mechanism of resistance of certain tumours against chemotherapeutic drugs. The myocardial perfusion imaging agent 99Tcm-sestamibi is a substrate for Pgp. Further characterization of 99Tcm-sestamibi has now been carried out in the transplantable rat breast adenocarcinoma cell line, MatB, and its doxorubicin-resistant variant, AdrR. In vitro accumulation of the tracer in wild-type (WT) MatB was high and was not affected by the Pgp modulator, PSC833. Conversely, AdrR cells did not accumulate significant amounts of tracer unless PSC833 was present. Imaging studies in rats bearing MatB-WT and AdrR tumours showed that 99Tcm-sestamibi washed out of the resistant tumours at three times the rate of WT tumours. These results support the potential use of 99Tcm-sestamibi for functional imaging of Pgp activity in patients undergoing chemotherapy.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Resistência a Múltiplos Medicamentos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Tecnécio Tc 99m Sestamibi , Animais , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/genética , Feminino , Variação Genética , Neoplasias Mamárias Experimentais/genética , Cintilografia , Ratos , Células Tumorais Cultivadas
10.
Arch Otolaryngol Head Neck Surg ; 121(2): 172-5, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7840925

RESUMO

OBJECTIVE: To evaluate the significance of positive surgical margins after vertical hemilaryngectomy for squamous cell carcinoma of the larynx. DESIGN: A retrospective review of patients undergoing hemilaryngectomy over a 20-year period. SETTING: A major academic medical center. PATIENTS: Fifty-six consecutive patients who underwent hemilaryngectomy between 1970 and 1990. Seventeen patients were excluded because of insufficient data or because they received postoperative radiation therapy. RESULTS: Eleven (28%) of 39 patients had cancer involvement of at least one margin. Two (8%) of 28 patients with negative margins and six (55%) of 11 patients with positive margins had recurrence. This difference in tumor recurrence is statistically significant. The mean disease-free interval prior to recurrence was 25 months, with no significant difference between the two groups. The mean follow-up periods for patients with positive vs negative margins were not statistically significant. There were no significant differences in survival estimates between patients with positive margins and those with negative margins. CONCLUSIONS: Despite a sevenfold increase in tumor recurrence rates for patients with positive margins after hemilaryngectomy, there was no adverse effect on overall survival when these patients were managed with close follow-up and salvage surgery with or without postoperative radiation therapy for tumor recurrence.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Laríngeas/cirurgia , Laringectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Taxa de Sobrevida
11.
J Pharm Sci ; 83(8): 1077-80, 1994 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7983589

RESUMO

Flurbiprofen is a chiral 2-arylpropionate used clinically as a racemate. Previously a significant pharmacokinetic interaction between the enantiomers of flurbiprofen has been reported in both rats and humans. The possible mechanism for this interaction was believed to involve competitive protein binding between the enantiomers. In addition, the saturable binding of flurbiprofen enantiomers in vitro in human plasma has been demonstrated. In this study different doses of racemic flurbiprofen were administered to rats to create differing extents of competition for protein binding sites between the enantiomers. There was a statistically significant dose-dependent increase in total body clearance and volume of distribution of both the R and S enantiomers. However, there was no change in either the S/R AUC ratio or the elimination rate constants for (R)- or (S)-flurbiprofen with increasing dose. These results are consistent with the hypothesis that the increasing amount of (R)- and (S)-flurbiprofen in the body causes displacement of flurbiprofen enantiomers from their protein binding sites, resulting in their increased total body clearance and volume of distribution. Further, the data suggest that previously reported extents of R to S enantiomeric inversion for other 2-arylpropionates may not be accurate if the enantiomers exhibit nonlinear kinetics or there is a significant kinetic interaction between the enantiomers.


Assuntos
Flurbiprofeno/farmacocinética , Animais , Ligação Competitiva/efeitos dos fármacos , Flurbiprofeno/administração & dosagem , Técnicas In Vitro , Injeções Intravenosas , Masculino , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Análise de Regressão , Estereoisomerismo
12.
J Anim Sci ; 71(9): 2412-9, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8407653

RESUMO

Loins from 12 carcasses of Small minus marbling and loins from 12 carcasses of Slight minus marbling were selected. Steaks from these loins were either completely trimmed of external fat or trimmed to .6 cm of external fat. Steaks were cooked to 67 degrees C either by a rapid, high-temperature broiler-grill or by a slower, lower temperature electric broiler. Muscle on the dorsal side of steaks (where fat trimming was performed) was used for shear force measurements (five separate core locations), and the ventral portion was used for sensory evaluation of tenderness. Sensory scores for tenderness were affected (P < .05) by various first-order interactions, although differences were minimal. Steaks of Slight minus marbling cooked by broiler-grilling had reduced tenderness scores. Only when steaks were cooked by broiler-grilling did complete fat removal produce cores that appeared more well-done. Broiler-grilling produced more well-done cores than did electrical broiling. Correlations between shear force expressed as peak load and tenderness scores were highest in cores that were more similar in degree of doneness to sensory evaluation samples. Although broiler-grilling produced considerable within-steak variation in degree of doneness, some of the highest correlations between shear core degree of doneness and peak load and between peak load and sensory tenderness were obtained with this broiling procedure. This would imply that rapid broiling is important in creating uniform tenderness in loin steaks of reduced fat, but further modifications in rapid broiling cookery are necessary to improve uniformity of cooked meat color.


Assuntos
Culinária , Carne/normas , Animais , Bovinos , Fatores de Tempo
13.
Head Neck ; 13(5): 420-3, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1938359

RESUMO

Sixty-eight patients were studied prospectively with serial thyroid-stimulating hormone (TSH) levels after radiotherapy for head and neck neoplasms. Overall, 57% of the patients developed elevated TSH levels. Excluding patients with less than 2 years follow-up, 85% developed an elevated TSH. Ninety-two percent of patients treated with partial thyroidectomy and radiotherapy developed an elevated TSH. Most TSH elevations occurred within 1 year of treatment. The dose of radiotherapy used and the performance of hemithyroidectomy were related to the development of elevated TSH levels (p less than 0.05). The performance of radical neck dissection, gender, hyperfractionated radiotherapy and the use of chemotherapy were not related to the development of an elevated TSH (p greater than 0.05).


Assuntos
Neoplasias de Cabeça e Pescoço/sangue , Tireotropina/sangue , Terapia Combinada , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Hipotireoidismo/etiologia , Masculino , Radioterapia/efeitos adversos , Estudos Retrospectivos
14.
J Anim Sci ; 69(9): 3523-32, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1938639

RESUMO

Effects of management system, ewe breed, sex, and legume grazing on cooking and sensory characteristics and shear force of lamb meat were estimated from data collected on animals produced in three management systems. System 1 lambs were born in late fall and fed to slaughter on a concentrate diet. System 2 lambs were born in January and February and grazed pure stands of alfalfa or ladino clover after weaning. System 3 lambs were born in March and April and remained with their dams on native bluegrass-white clover pasture throughout the grazing season. Lambs were progeny of either 1/2-Suffolk, 1/2-Rambouillet ewes or 1/2-Suffolk, 1/4-Finnsheep, 1/4-Rambouillet or Dorset ewes and were sired by Suffolk rams. Lambs were slaughtered at 50 (females) to 55 kg (males). One-half of the males in System 1 were left intact; all males in Systems 2 and 3 were castrated. Mean age at slaughter was 156, 204, and 234 d for lambs in Systems 1, 2, and 3, respectively. Cooked weight of loin chops averaged 68.5% of uncooked weight and did not differ among systems. Shear force was greatest for System 1 lambs and least for System 3 lambs in yr 1, but systems did not differ in shear performance in yr 2. System differences in tenderness favored System 3 lambs. Although mean flavor intensity was least for System 2 lambs, the frequency of high-intensity, potentially objectionable flavors was highest for these lambs and especially for those grazing alfalfa. In general, however, sensory characteristics did not differ greatly among production systems, and correlation analysis revealed little potential to use carcass traits to predict meat characteristics.


Assuntos
Criação de Animais Domésticos , Cruzamento , Carne/normas , Ovinos/crescimento & desenvolvimento , Ração Animal , Animais , Feminino , Masculino , Estações do Ano , Ovinos/anatomia & histologia , Ovinos/genética
15.
Biopharm Drug Dispos ; 12(6): 435-45, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1932607

RESUMO

In this randomized, crossover study comparing the bioavailability of a film-coated (Ansaid) with a sugar-coated (Froben) 100 mg tablets of racemic flurbiprofen in 23 healthy young men, no significant differences were found for Cmax, tmax or AUC, using a nonstereoisomeric assay for flurbiprofen. Minor differences in the appearance of flurbiprofen in serum during the first 30-min post-dosing period were noted, with Ansaid appearing earlier than Froben. These differences likely reflect dissolution rate dissimilarity between the two products. Stereospecific determinations demonstrate a small (7.8 per cent) but significant difference in AUC of the active S-configuration (Froben greater than Ansaid). No significant differences between Ansaid and Froben were found for tmax or Cmax for the S-flurbiprofen. In bioequivalency studies of chiral drugs, stereospecific approaches provide a more accurate assessment of products.


Assuntos
Flurbiprofeno/farmacocinética , Adolescente , Adulto , Disponibilidade Biológica , Flurbiprofeno/administração & dosagem , Humanos , Masculino , Estereoisomerismo
16.
J Pharmacol Exp Ther ; 258(2): 695-701, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1865366

RESUMO

Fenoprofen (FN), a member of the 2-arylpropionic acid (2-APA) class of nonsteroidal anti-inflammatory drugs is administered clinically as a racemate. In humans, FN has been shown to rapidly undergo substantial in vivo unidirectional chiral inversion with the inactive R-isomer converted to its active antipode. As with any p.o. administered drug, before reaching the systemic circulation. FN may undergo first-pass metabolism, the major organs involved being the gastrointestinal tract and/or the liver. The site(s) of inversion for the 2-APAs have been a subject of debate, with presystemic intestinal metabolism in humans and hepatic systemic metabolism in rats receiving the most attention. The inversion of R-FN was studied in the male Sprague-Dawley rat 1) in vivo after p.o. and i.v. administration of racemic-FN and R-FN, 2) after perfusion of R-FN into isolated liver (single-pass and recirculation) and 3) after a 2-hr incubation with everted intestinal tissue (duodenum, jejunum, ileum and colon) and noneverted stomach pouch. The enantiomers and their acyl-glucuronides were quantitated using a previously developed stereospecific assay. With the isolated liver, R-FN was shown to invert in both the single-pass and recirculation systems, with a first-pass extraction ratio of 0.3. A significant but variable inversion in all intestinal segments was observed. Substantial inversion by the duodenum was observed (serosal S:R ratio, 1.2) with maximal inversion by the jejunum (serosal S:R ratio, 2.2), whereas inversion of R-FN was absent in the stomach. Considerable glucuronidation was observed in all tissues studied including first-pass glucuronidation of both enantiomers after single-pass perfusion through the isolated liver and stereoselective glucuronidation in intestinal tissue segments. The results indicate that, in the male Sprague-Dawley rat, R-FN undergoes presystemic inversion by both the gastrointestinal tract and liver. These results, however, must be viewed with caution as they may not necessarily be extrapolated to other 2-APAs or species.


Assuntos
Fenoprofeno/metabolismo , Animais , Glucuronatos/metabolismo , Ibuprofeno/metabolismo , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Masculino , Perfusão , Ratos , Ratos Endogâmicos , Estereoisomerismo
17.
J Pharm Sci ; 78(8): 632-4, 1989 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2778668

RESUMO

Flurbiprofen [FL, (+/-)-2-(2-fluoro-4-biphenylyl)propionic acid] is a 2-arylpropionic acid nonsteroidal anti-inflammatory drug which is commercially available as a racemate. The anti-inflammatory activity of FL, however, appears to be mainly due to the S enantiomer. Recently, it has been postulated that, in both humans and rats, the two enantiomers of FL may interact when racemic doses are given. This study examines the above postulate in the rat by administration of single iv doses of racemic FL (10 mg/kg), and R- and S-FL (5 mg/kg of each). Plasma concentrations (0-12 h) of the enantiomers were measured using a stereospecific HPLC assay. A significant interaction was noticed between the enantiomers: mean AUC +/- SD of R-FL was reduced from 115.3 +/- 21.3 to 49.0 +/- 10.4 mg/L.h as a result of S-FL coadministration. A trend towards reduced S-FL plasma concentration was also evident when the enantiomer was given as the racemate [mean AUC +/- SD; 176.8 +/- 37.7 racemate versus 241.4 +/- 86.2 mg/L.h alone]. The reduction in S-FL, however, was not significant due perhaps to the observed interanimal variation. While the enantiomeric interaction caused a significant enlargement of the volume of distribution of R-FL, it failed to alter the terminal half-life of the enantiomer. It is suggested that the interaction is a result of displacement from plasma protein binding sites of one enantiomer by the other.


Assuntos
Flurbiprofeno/farmacocinética , Propionatos/farmacocinética , Animais , Meia-Vida , Masculino , Ratos , Ratos Endogâmicos , Estereoisomerismo , Fatores de Tempo
18.
J Neurochem ; 51(4): 1176-83, 1988 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2458433

RESUMO

We studied the properties of the N18-RE-105 neuronal cell line to determine if its glutamate binding site represents a neurotransmitter receptor. In immunocytochemical experiments, these cells stained strongly for neurofilament, but not for glial fibrillary acidic protein. In whole-cell patch clamp experiments, cells exhibited voltage-dependent Na+, Ca2+, and K+ currents characteristic of neurons. However, perfusion with L-glutamate or other excitatory amino acids did not evoke the inward current expected of a receptor/channel complex. In binding studies, the maximum accumulation of L-[3H]glutamate by washed membrane vesicles at 37 degrees C was 69 pmol/mg protein, and half-maximal accumulation occurred at 0.64 microM. This accumulation was blocked completely by quisqualate, partially by DL-2-amino-4-phosphonobutyric acid and L-cystine, but not at all by 1 mM kainate or N-methylaspartate. L-[3H]Glutamate accumulation was stimulated by Cl-, but reduced by Na+, 0.01% digitonin, or hyperosmotic (400 mM glucose) assay medium. The release of L-[3H]glutamate from vesicles was much faster in the presence of 100 microM unlabelled glutamate than 100 microM unlabelled quisqualate or DL-2-amino-4-phosphonobutyric acid. Thus, although N18-RE-105 cells possess many neuronal properties, the results obtained are not those expected from reversible binding of L-glutamate to a receptor/channel complex, but are consistent with a Cl- -stimulated sequestration or exchange process.


Assuntos
Glutamatos/metabolismo , Células Híbridas/metabolismo , Canais Iônicos/metabolismo , Neuroblastoma/metabolismo , Receptores de Neurotransmissores/metabolismo , Aminobutiratos/farmacologia , Animais , Ligação Competitiva , Cálcio/metabolismo , Cloretos/farmacologia , Cistina/metabolismo , Cistina/farmacologia , Condutividade Elétrica , Imunofluorescência , Glutamatos/farmacologia , Ácido Glutâmico , Proteínas de Filamentos Intermediários/análise , Camundongos , Proteínas de Neurofilamentos , Neurônios/metabolismo , Oxidiazóis/metabolismo , Oxidiazóis/farmacologia , Potássio/metabolismo , Ácido Quisquálico , Ratos , Receptores de Glutamato , Sódio/metabolismo , Células Tumorais Cultivadas
19.
J Pharm Sci ; 77(8): 666-9, 1988 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3210154

RESUMO

Flurbiprofen, a 2-arylpropionic acid (2-APA) nonsteroidal anti-inflammatory drug (NSAID), exists as racemate and is used as such. Although the activity of 2-APAs is due mainly to their S-enantiomers, information on the pharmacokinetics of flurbiprofen is usually based on the measurement of total concentrations of S- and R-flurbiprofen. In this work, the pharmacokinetics of flurbiprofen enantiomers following single doses were studied in humans and rats. Upon iv administration of 10 mg/kg of racemic flurbiprofen to male Sprague-Dawley rats, the plasma concentrations were consistently higher for S-flurbiprofen than for R-flurbiprofen (AUC = 134 +/- 39 versus 41 +/- 9 mg.L-1 h). In bile duct-cannulated rats, the biliary excretion contained only 3.6-5.2% of the dose as conjugated flurbiprofen (S:R = 1.2-2.1). After administration of R-flurbiprofen to the rat, both enantiomers were found in plasma [AUC(R):AUC(S) = 0.10-0.16], indicating a limited extent of enantiomeric bioinversion. This is consistent with the previously reported limited extent of flurbiprofen uptake into fat. In healthy volunteers also, significant stereoselectivity was observed in the plasma concentration of the drug after 100-mg oral racemic doses [AUC-(S):AUC(R) = 45.4 +/- 12.7:40.1 +/- 14.3 mg.L-1.h]. As compared with the R-enantiomer, S-flurbiprofen has a smaller volume of distribution (7.23 +/- 1.9 versus 8.41 +/- 3.0 L) and total clearance (1.23 +/- 0.34 versus 1.47 +/- 0.50 L/h), but an equal half-life (4.21 +/- 1.2 versus 4.18 +/- 1.3 h). In urine, on the other hand, the R-configuration was predominant, as greater amounts of the R-enantiomer were found both as conjugated flurbiprofen and as an unidentified metabolite. Negligible amounts of intact flurbiprofen enantiomers were detected in urine. The observed stereoselectivity in humans cannot be attributed to enantiomeric bioinversion, as S-flurbiprofen was not detected in plasma and urine after oral administration of R-flurbiprofen.


Assuntos
Flurbiprofeno/farmacocinética , Propionatos/farmacocinética , Administração Oral , Adulto , Animais , Bile/metabolismo , Feminino , Flurbiprofeno/administração & dosagem , Meia-Vida , Humanos , Masculino , Ratos , Ratos Endogâmicos , Especificidade da Espécie , Estereoisomerismo
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