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1.
Animal ; 15(11): 100381, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34757288

RESUMO

The increasing demand for natural products is currently transforming the meat industry, making grass-fed and finished beef a valuable option for improving profits. However, the transformation of conventional operations to grass-fed systems comprises many modifications, such as logistical, technological, and financial that could be very complex and expensive, involving economic risk. Therefore, in this study, we analyzed the growth curve, critical economic traits, and carcass quality and finished characteristics over several consecutive years in closely related grass-fed and finished Angus steers, to reduce the genetic effect on the results. We found that grass-fed steers require around 188 additional days to reach the market weight (approx. 470 kg) and had approximately 70% less average daily gain compared to the grain-fed and finished steers. Regression analysis demonstrated an interaction between feed and age (P < 0.01); thus, individual regressions were fitted for each regimen style, obtaining almost perfect linear curves for both treatments, which could be straightforwardly used in practical situations due to its simplicity. Six of eight carcass traits were different between grain-fed and grass-fed and finished steers. Hot-carcass weight, dressing, back fat, and quality grade were superior in grain-fed individuals, contrarily to yield grade and ribeye area/carcass ratio, which were better in grass-fed and finished steers (P < 0.05). Interestingly, the meat tenderness was certainly low and similar in both treatments (P = 0.25), indicating the feasibility of producing tender meat with animals under a grass-fed diet. Nevertheless, according to the quality grade analysis, grain-fed carcasses were greater ranked compared to grass-fed bodies (P < 0.01), regardless of their same tenderness. The results will provide valuable information for better understanding beef cattle in grass-feeding finishing systems, especially from weaning to harvest. Additionally, the study will expand the knowledge about the quality of meat obtained from animals that received grass exclusively, becoming relevant information for economic evaluation and management decisions for grass-based cattle operations.


Assuntos
Ração Animal , Carne , Ração Animal/análise , Animais , Composição Corporal , Bovinos , Dieta/veterinária , Grão Comestível , Carne/análise
2.
Curr Mol Med ; 18(1): 65-70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29879886

RESUMO

BACKGROUND: Dopamine physiological functions make dopaminergic genes suitable candidates for association studies in eating disorders (ED). A Val158Met polymorphism in the catechol-O-methyltransferase (COMT) gene, which is involved in dopamine degradation, has been studied in relation to ED. OBJECTIVE: We aimed to analyze the association between this polymorphism and general psychopathological symptoms that are often coupled to these disorders. METHOD: A total of 303 ED patients, diagnosed according to DSM-5 criteria, completed the SCL-90R questionnaire and were genotyped for the Val158Met polymorphism. RESULTS: There were significant differences in the global indices of the SCL-90R inventory between the three ED groups (Anorexia Nervosa (AN), Bulimia Nervosa (BN) and binge-eating disorder; ANOVA-p < 0.05). Females with BN showed the highest scores (worse symptomatology) of all participants. In this group, a gene-dose effect was observed on the psychometric evaluation of the patients, as Val/Val carriers displayed the highest scores for all the SCL-90R scales, followed by Val/Met and then Met/Met carriers. Significant differences between genotypes were observed in the Obsessive- Compulsive (p = 0.018), Paranoid Ideation (p = 0.0005) and Psychoticism (p = 0.039) scales, as well as in the PSDI (p = 0.014) general index. CONCLUSION: The results taken together suggest that COMT genetic variability may contribute to general psychopathological symptoms in patients with BN.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia Nervosa , Catecol O-Metiltransferase/genética , Predisposição Genética para Doença , Polimorfismo Genético , Adolescente , Adulto , Substituição de Aminoácidos , Anorexia Nervosa/genética , Anorexia Nervosa/psicologia , Transtorno da Compulsão Alimentar/genética , Transtorno da Compulsão Alimentar/psicologia , Bulimia Nervosa/genética , Bulimia Nervosa/psicologia , Criança , Feminino , Humanos , Mutação de Sentido Incorreto , Psicometria
3.
J Nonlinear Sci ; 28(1): 235-268, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29367810

RESUMO

We provide a numerical study of the macroscopic model of Barré et al. (Multiscale Model Simul, 2017, to appear) derived from an agent-based model for a system of particles interacting through a dynamical network of links. Assuming that the network remodeling process is very fast, the macroscopic model takes the form of a single aggregation-diffusion equation for the density of particles. The theoretical study of the macroscopic model gives precise criteria for the phase transitions of the steady states, and in the one-dimensional case, we show numerically that the stationary solutions of the microscopic model undergo the same phase transitions and bifurcation types as the macroscopic model. In the two-dimensional case, we show that the numerical simulations of the macroscopic model are in excellent agreement with the predicted theoretical values. This study provides a partial validation of the formal derivation of the macroscopic model from a microscopic formulation and shows that the former is a consistent approximation of an underlying particle dynamics, making it a powerful tool for the modeling of dynamical networks at a large scale.

4.
AJNR Am J Neuroradiol ; 33(7): 1349-55, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22322613

RESUMO

BACKGROUND AND PURPOSE: Both IDH1 mutation and MGMT promoter methylation are associated with longer survival. We investigated the ability of imaging correlates to serve as noninvasive biomarkers for these molecularly defined GBM subtypes. MATERIALS AND METHODS: MR imaging from 202 patients with GBM was retrospectively assessed for nonenhancing tumor and edema among other imaging features. IDH1 mutational and MGMT promoter methylation status were determined by DNA sequencing and methylation-specific PCR, respectively. Overall survival was determined by using a multivariate Cox model and the Kaplan-Meier method with a log rank test. A logistic regression model followed by ROC analysis was used to classify the IDH1 mutation and methylation status by using imaging features. RESULTS: MGMT promoter methylation and IDH1 mutation were associated with longer median survival. Edema levels stratified survival for methylated but not unmethylated tumors. Median survival for methylated tumors with little/no edema was 2476 days (95% CI, 795), compared with 586 days (95% CI, 507-654) for unmethylated tumors or tumors with edema. All IDH1 mutant tumors were nCET positive, and most (11/14, 79%) were located in the frontal lobe. Imaging features including larger tumor size and nCET could be used to determine IDH1 mutational status with 97.5% accuracy, but poorly predicted MGMT promoter methylation. CONCLUSIONS: Imaging features are potentially predictive of IDH1 mutational status but were poorly correlated with MGMT promoter methylation. Edema stratifies survival in MGMT promoter methylated but not in unmethylated tumors; patients with methylated tumors with little or no edema have particularly long survival.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/diagnóstico , Glioblastoma/genética , Isocitrato Desidrogenase/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Edema Encefálico/diagnóstico , Edema Encefálico/genética , Edema Encefálico/mortalidade , Neoplasias Encefálicas/mortalidade , California/epidemiologia , Comorbidade , Metilação de DNA/genética , Feminino , Marcadores Genéticos/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Glioblastoma/mortalidade , Humanos , Incidência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Estatística como Assunto , Análise de Sobrevida , Taxa de Sobrevida
5.
Eur J Clin Microbiol Infect Dis ; 31(3): 243-50, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21647616

RESUMO

Respiratory syncytial virus (RSV) is the viral agent which is more frequently involved in lower respiratory tract infections (LRTIs) in infants under 1 year of age in developed countries. A new oligochromatographic assay, Speed-Oligo® RSV, was designed and optimized for the specific detection and identification of RSV subtypes A and B. The test was evaluated in 289 clinical samples from 169 hospitalized children using an immunochromatography (IC) test, virus isolation by culture, and an in-house real-time polymerase chain reaction (RT-PCR). Other viruses causing LRTIs were investigated by cell culture or PCR-based tests. Sixty-two patients were infected by RSV (36.7%). In addition, adenovirus, influenza B, parainfluenza 2, and human metapneumovirus were detected in rates ranging from 5 to 8%. A proportion of 10.1% of the patients had mixed infections. The sensitivity, specificity, and positive and negative predictive values were, respectively, 94.9, 99.4, 98.9, and 97.4% for Speed-Oligo® RSV, 92.9, 96.3, 92.9, and 96.3% for RT-PCR/RSV, and 58.4, 98.1, 93.3, and 82.6% for IC. Our rates of viral detection and co-infection were similar to those of previously reported series. Finally, we find that Speed-Oligo® RSV is a rapid and easy-to-perform technique for the detection of RSV and the identification of subtypes A and B.


Assuntos
Bronquiolite Viral/diagnóstico , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sincicial Respiratório Humano/genética , Adolescente , Bronquiolite Viral/virologia , Criança , Criança Hospitalizada , Pré-Escolar , Técnicas de Diagnóstico do Sistema Respiratório , Hospitalização , Humanos , Lactente , Recém-Nascido , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , RNA Viral/análise , RNA Viral/genética , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e Especificidade
6.
J Anim Sci ; 88(1): 87-95, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19820066

RESUMO

The effect of individual and dam (maternal) inbreeding was quantified for preweaning traits in an Angus nucleus herd that has been closed to outside breeding for 70 yr. The effectiveness of 5 models (linear, quadratic, exponential, Michaelis-Menten, and Rumford-Newton) was evaluated for describing the effect of inbreeding on growth traits, hock length (HL), and scrotal circumference (SC). Pedigree information and production records were retrieved for 10,938 animals and analyzed in an animal model that included the fixed effects of year of birth, age of the dam, sex, and age at weaning (for traits measured at weaning). Average individual and maternal inbreeding in the herd were 0.068 and 0.066, respectively, for all animals; in the last calf crop these values were 0.120 for the calves and 0.121 for their dams. Inbreeding depression was observed for BW at birth (WB), weaning weight (WW), BW adjusted to 205 d of age (W205), ADG, HL, and SC. The effect of maternal inbreeding was smaller than for individual inbreeding for WB, WW, W205, and ADG. Nonlinear prediction was done more effectively by the exponential and Michaelis-Menten models. Quadratic polynomials were an inadequate descriptor of inbreeding effects. Genetic gain from selection at an intensity equivalent to 0.25 can be nullified by an inbreeding accumulation of 0.187 (WB), 0.056 (WW), 0.068 (W205), 0.065 (ADG), or 0.092 (SC). Inbreeding accumulation of 0.018 is required to nullify genetic gain for HL; this particular prediction is valid for non-inbred cows due to an observed interaction between individual and maternal inbreeding. At current inbreeding accumulation levels in this herd, 7 generations of inbreeding accumulation will be necessary to nullify the genetic progress from 1 generation of selection in growth traits.


Assuntos
Bovinos/genética , Bovinos/fisiologia , Endogamia , Animais , Animais Lactentes , Peso ao Nascer , Feminino , Masculino , Parto , Seleção Genética , Fatores de Tempo , Desmame , Aumento de Peso
7.
Clin Microbiol Infect ; 15(5): 473-80, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19302698

RESUMO

An incorrect or late diagnosis can lead to an increase in the morbidity and mortality caused by pneumonia, and the availability of a rapid and accurate microbiological test to verify the aetiology is imperative. This study evaluated a molecular test for the identification of the bacterial cause of atypical community-acquired pneumonia (ACAP). Fifty-four children with pneumonia were studied using bacteriological cultures, Mycoplasma pneumoniae, Coxiella burnetii, Chlamydophila pneumoniae and Legionella spp. serology, and Streptococcus pneumoniae and Legionella antigens. Simultaneously, the presence of bacterial and fungal DNA was tested for in respiratory secretion samples using the Vircell SL kit, including multiplex PCR and amplicon detection by means of line blots. There were 14 cases of ACAP caused by M. pneumoniae, with positive kit results for 13 of them, and two cases of Q-fever, with negative kit results for Coxiella burnetii. The test was negative in the remaining 38 cases (one staphylococcal pneumonia, 20 Streptococcus pneumoniae pneumonias, and 17 probable viral pneumonias). The sensitivity of the test for the detection of M. pneumoniae was 92.8% and the specificity was 100%. The Vircell SL kit allows detection of M. pneumoniae DNA in respiratory secretion samples from children with ACAP.


Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Infecções Comunitárias Adquiridas/microbiologia , DNA Bacteriano/genética , Técnicas de Diagnóstico Molecular/métodos , Pneumonia Bacteriana/diagnóstico , Adolescente , Bactérias/genética , Secreções Corporais/microbiologia , Criança , Pré-Escolar , DNA Fúngico/genética , Feminino , Humanos , Lactente , Masculino , Sensibilidade e Especificidade
8.
Drug Metab Lett ; 1(1): 3-5, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19356010

RESUMO

We investigated the role of NAT2 on clonazepam acetylation, using transiently expressed human NAT2 alleles. The NAT25*B and the NAT2*6A variant alleles cause a 20 and 22-fold reduction in the Vmax, respectively. We conclude that NAT2 is responsible for 7-aminoclonazepam acetylation and that NAT2 gene polymorphisms impair such metabolic pathway.


Assuntos
Arilamina N-Acetiltransferase/metabolismo , Clonazepam/análogos & derivados , Clonazepam/metabolismo , Acetilação , Alelos , Animais , Arilamina N-Acetiltransferase/genética , Células COS , Chlorocebus aethiops , Humanos , Farmacogenética , Polimorfismo Genético , Transfecção
9.
Cytogenet Genome Res ; 105(1): 83-92, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15218262

RESUMO

Analyzing the satellite DNA in the ant species Monomorium subopacum we found two unrelated families of satellite DNA. Because these satellite DNA families were isolated using the two enzymes HaeIII and EcoRI we called the two families HaeIII and EcoRI family, respectively. The HaeIII family proved to be organized in a 135-bp basic unit repeat, the EcoRI family in a 2.5-kb basic unit repeat. The latter represents perhaps the longest satellite DNA isolated up to now in insects. The HaeIII family apparently comprises about 10% of the total genomic DNA whereas the EcoRI family represents only about 1-2%. A comparative analysis of the two satellite DNA sequences showed no homology between the two families although both sequences possessed long A and T stretches. Eight of the 34 chromosomes showed hybridization with the HaeIII family and hybridization signals are visible in six chromosomes with the EcoRI family. Analysis of the electrophoretic mobility of satellite DNA on non-denaturing polyacrylamide showed that the HaeIII family is only slightly curved. However, the unit of the EcoRI satellite DNA family has curvature, especially the first 1000 bp of the monomeric repeat, in which this DNA is AT rich and has numerous A and T stretches. There are also internal inverted subrepeats in each family. The sequences of satellite DNA families found in Monomorium subopacum are different from the sequences of other satellite DNAs cloned in insects, including other species of ants.


Assuntos
Formigas/genética , DNA Satélite/isolamento & purificação , Sequências Repetitivas de Ácido Nucleico , Animais , Sequência de Bases , Southern Blotting , Clonagem Molecular , DNA , Enzimas de Restrição do DNA/metabolismo , DNA Satélite/genética , Cariotipagem , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Alinhamento de Sequência
10.
J Hered ; 93(4): 282-5, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12407216

RESUMO

To determine the telomere sequence in Tapinoma nigerrimum, we carried out in situ hybridization using TTAGGG and TTAGG repeat polymerase chain reaction (PCR)-generated probes. No hybridization signals were found when TTAGGG was used as a probe. However, strong signals were observed at the end of the chromosomes with the TTAGG probe. Southern blot analysis carried out on genomic DNA using TTAGG as a probe showed a strong hybridization signal even under highly stringent conditions. Similar results were obtained in Southern blot analysis carried out on genomic DNA of 19 species of ants belonging to three different subfamilies. In accordance with all the results shown in this article, the TTAGG repeat seems to be the major component of the telomere sequence in the majority of ant species.


Assuntos
Formigas/genética , Sequência Conservada , Telômero/genética , Animais , Sequência de Bases , Abelhas/genética , Southern Blotting
11.
Cytogenet Genome Res ; 98(4): 302-7, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12826758

RESUMO

In this paper the satellite DNA (stDNA) of the phytophagous beetle Xanthogaleruca luteola is analyzed. It is organized in a tandem repeat of 149-bp-long monomers, has an AT content of 59%, and presents inverted internal repeats. Restriction analysis of the total DNA with methylation-sensitive enzymes suggests that this repetitive DNA is not methylated. Analysis of the electrophoretic mobility of stDNA on non-denaturing polyacrylamide gels showed that this stDNA is not curved. In situ hybridization with a biotinylated probe of the stDNA revealed a pericentromeric localization of these sequences in the majority of the meiotic bivalents. We have studied the stDNA of X. luteola from two populations with very distinct geographical origins. The sequence and phylogenetic analysis of monomers from these two populations showed that the repetitive element is conserved within the species. Putative gene conversion tracts are identified when the different monomers of the same population are compared. These results could indicate the existence of processes of homogenization that would extend these mutations to all the satellite repeats.


Assuntos
Besouros/genética , DNA Satélite/genética , Filogenia , Animais , Sequência de Bases , Clonagem Molecular , Sequência Consenso , Metilação de DNA , Dados de Sequência Molecular , Ulmus
12.
Hereditas ; 134(1): 73-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11525067

RESUMO

Two families of repeated DNA sequences were cloned from Olea europaea ssp sativa cv. "Picual". The first repetitive DNA is organized in a tandem repeat of monomers of 178 bp. Sequencing of several clones showed that it is relatively A-T rich (54.49%) and possesses short direct and inverted subrepeats as well as some palindromic sequences. Comparison between the monomers revealed heterogeneity of the sequence primary structure. This repetitive DNA is present in several cultivars of olive cultivates. Comparison of sequences with other repetitive DNAs described in Olea europaea has been carried out. No significant similarity was found. All the obtained results suggest that this repetitive DNA described here is a new family of repetitive DNA. The second repetitive DNA is organized in a tandem repeat of monomers of 78 bp. This second family of repetitive DNA showed significant similarity with other repetitive DNAs previously described in Olea europaea. Their existence in new cultivars of olive is shown.


Assuntos
DNA de Plantas/genética , Plantas Comestíveis/genética , Sequências de Repetição em Tandem , Sequência de Bases , Southern Blotting , Clonagem Molecular , Sequência Consenso , Dados de Sequência Molecular , Folhas de Planta/química , Plantas Comestíveis/classificação , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
13.
Cienc. ginecol ; 4(6): 287-289, nov. 2000. ilus, tab
Artigo em Es | IBECS | ID: ibc-11454

RESUMO

Una causa frecuente de dolor abdominal cíclico en pacientes adolescentes que todavía no han menstruado es el hematocolpos, generalmente secundario a himen imperforado. Presentamos el caso poco habitual de una adolescente con útero doble y hematocolpos que consultó por dolor abdominal cíclico con menstruaciones regulares (AU)


Assuntos
Adolescente , Feminino , Humanos , Útero/anormalidades , Vagina/anormalidades , Rim/anormalidades , Hematocolpia/complicações , Doenças dos Genitais Femininos/complicações , Doenças dos Genitais Femininos , Hematocolpia
14.
Clin Pharmacokinet ; 39(2): 127-53, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10976659

RESUMO

Caffeine from dietary sources (mainly coffee, tea and soft drinks) is the most frequently and widely consumed CNS stimulant in the world today. Because of its enormous popularity, the consumption of caffeine is generally thought to be safe and long term caffeine intake may be disregarded as a medical problem. However, it is clear that this compound has many of the features usually associated with a drug of abuse. Furthermore, physicians should be aware of the possible contribution of dietary caffeine to the presenting signs and symptoms of patients. The toxic effects of caffeine are extensions of their pharmacological effects. The most serious caffeine-related CNS effects include seizures and delirium. Other symptoms affecting the cardiovascular system range from moderate increases in heart rate to more severe cardiac arrhythmia. Although tolerance develops to many of the pharmacological effects of caffeine, tolerance may be overwhelmed by the nonlinear accumulation of caffeine when its metabolism becomes saturated. This might occur with high levels of consumption or as the result of a pharmacokinetic interaction between caffeine and over-the-counter or prescription medications. The polycyclic aromatic hydrocarbon-inducible cytochrome P450 (CYP) 1A2 participates in the metabolism of caffeine as well as of a number of clinically important drugs. A number of drugs, including certain selective serotonin reuptake inhibitors (particularly fluvoxamine), antiarrhythmics (mexiletine), antipsychotics (clozapine), psoralens, idrocilamide and phenylpropanolamine, bronchodilators (furafylline and theophylline) and quinolones (enoxacin), have been reported to be potent inhibitors of this isoenzyme. This has important clinical implications, since drugs that are metabolised by, or bind to, the same CYP enzyme have a high potential for pharmacokinetic interactions due to inhibition of drug metabolism. Thus, pharmacokinetic interactions at the CYP1A2 enzyme level may cause toxic effects during concomitant administration of caffeine and certain drugs used for cardiovascular, CNS (an excessive dietary intake of caffeine has also been observed in psychiatric patients), gastrointestinal, infectious, respiratory and skin disorders. Unless a lack of interaction has already been demonstrated for the potentially interacting drug, dietary caffeine intake should be considered when planning, or assessing response to, drug therapy. Some of the reported interactions of caffeine, irrespective of clinical relevance, might inadvertently cause athletes to exceed the urinary caffeine concentration limit set by sports authorities at 12 mg/L. Finally, caffeine is a useful and reliable probe drug for the assessment of CYP1A2 activity, which is of considerable interest for metabolic studies in human populations.


Assuntos
Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/farmacocinética , Citocromo P-450 CYP1A2/metabolismo , Medicamentos sem Prescrição/farmacocinética , Animais , Cafeína/sangue , Bebidas Gaseificadas , Estimulantes do Sistema Nervoso Central/sangue , Café/química , Dopagem Esportivo/prevenção & controle , Interações Medicamentosas/fisiologia , Humanos , Chá/química
15.
Ther Drug Monit ; 22(4): 409-17, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10942180

RESUMO

Twenty-five healthy volunteers were given 100 mg caffeine orally and several estimates of cytochrome P450 1A2 (CYP1A2) activity were evaluated. The validation was performed by correlation of different parameters in plasma, saliva, and urine to two measures of caffeine clearance, CL(oral) and CL(137X-->17X) that served as standards of reference. Two subjects were excluded because of noncompliance with a caffeine-free diet. In the remaining 23 subjects, both plasma and saliva total clearances of caffeine were highly correlated with each other (r(s) = 0.97, p < 0.0001). The ratio 17X/137X restricted to one sampling point taken 4 hours after dose, showed a high correlation (r(s)) with CL(oral) and CL(137X-->17X) in plasma (0.84/0.83) and saliva (0.82/0.77) (p < 0.0001 for all the correlation values) where 17X is 1,7-dimethylxanthine (paraxanthine) and 137X is 1,3,7-trimethylxanthine (caffeine). Additionally, the ratio (AFMU + 1U + 1X + 17U + 17X)/137X in a 0-24 hours urine sampling showed the highest correlation with CL(137X-->17X) (r(s) = 0.85, p < 0.001) where AFMU is 5-acetylamino-6-formylamino-3-methyluracil, 1U is 1-methyluracil, 1X is 1-methylxanthine, and 17U is 1,7-dimethyluric acid. The major estimates of CYP1A2 activity were significantly less in nonsmoking females, and this probably was related to the use of oral contraceptives in this subpopulation. In summary, among caffeine-based approaches for CYP1A2, the authors recommend either plasma or saliva 17X/137X ratio and the urinary (AFMU + 1U + 1X + 17U + 17X)/137X ratio during a sampling interval of at least 8 hours, starting at time zero since caffeine intake. These indices are simple, reliable, and relatively inexpensive estimates of CYP1A2 activity to be used in the study of human populations.


Assuntos
Cafeína/farmacocinética , Citocromo P-450 CYP1A2/metabolismo , Saliva/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Eur J Clin Pharmacol ; 56(2): 145-51, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10877009

RESUMO

OBJECTIVE: The aim of this study was to find whether endogenous substances could modulate CYP3A activity. There is evidence that CYP3A, a major phase-I xenobiotic metabolizing enzyme, is present in human brain but, at the present time, endogenous substrates for such an enzyme remain to be identified. A possible linkage between the CYP2D6 enzyme and serotonergic transmission has been recently reported by our group. In the same manner, structurally related enzymes such as CYP3A could also be related to endogenous compounds. METHODS: CYP3A activity was measured using the enzyme-specific substrate midazolam in human liver microsomes. Several neurotransmitters, precursors, and their metabolites, corresponding to three different metabolic routes, were assayed as putative modulators of CYP3A enzyme activity. These comprised serotonergic, catecolaminergic, and GABAergic transmitters and precursors. The inhibitory capacity of ketoconazole, a competitive inhibitor of CYP3A, was also analyzed for comparison. RESULTS: The kinetic analysis of the midazolam 1-hydroxylase activity measured in microsomes from five human liver samples indicated Km values (mean +/- SD) of 5.8 +/- 4.9 microM, and Vmax values of 1.7 +/- 1.4 nmol min(-1) per mg microsomal protein in all the samples used in the study. Of the 14 substances analyzed, adrenaline, serotonin, and 5-hydroxytriptofol were full inhibitors of CYP3A enzyme activity (Ki values of 42.3, 26.4, and 43 microM, respectively). The remaining substances were weak inhibitors or had no inhibitory effect. CONCLUSION: Brain CYP3A activity could be modulated by some neurotransmitters and precursors.


Assuntos
Hidrocarboneto de Aril Hidroxilases , Sistema Enzimático do Citocromo P-450/metabolismo , Epinefrina/metabolismo , Microssomos Hepáticos/metabolismo , Midazolam/metabolismo , Neurotransmissores/metabolismo , Oxirredutases N-Desmetilantes/metabolismo , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismo , Citocromo P-450 CYP3A , Inibidores Enzimáticos/farmacologia , Epinefrina/farmacologia , Humanos , Hidroxitriptofol/metabolismo , Hidroxitriptofol/farmacologia , Técnicas In Vitro , Cetoconazol/farmacologia , Microssomos Hepáticos/enzimologia , Neurotransmissores/farmacologia , Isoformas de Proteínas/metabolismo , Serotonina/farmacologia , Ácido gama-Aminobutírico/farmacologia
17.
J Clin Psychopharmacol ; 19(6): 494-9, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10587283

RESUMO

This study investigated to what extent fluvoxamine affects the pharmacokinetics of thioridazine (THD) in schizophrenic patients under steady-state conditions. Concentrations of THD, mesoridazine, and sulforidazine were measured in plasma samples obtained from 10 male inpatients, aged 36 to 78 years, at three different time points: A, during habitual monotherapy with THD at 88 +/-54 mg/day; B, after addition of a low dosage of fluvoxamine (25 mg twice a day) for 1 week; and C, 2 weeks after fluvoxamine discontinuation. After the addition of fluvoxamine, THD concentrations relative to time point A significantly increased approximately threefold from 0.40 to 1.21 micromol/L (225%) (p < 0.002), mesoridazine concentrations increased from 0.65 to 2.0 micromol/L (219%) (p < 0.004), and sulforidazine levels increased from 0.21 to 0.56 micromol/L (258%) (p < 0.004). The THD-mesoridazine and THD-sulforidazine ratios remained unchanged during the study. Mean plasma THD, mesoridazine, and sulforidazine levels decreased at time point C, but despite fluvoxamine discontinuation for 2 weeks, three patients continued to exhibit elevated concentrations of THD and its metabolites. In conclusion, fluvoxamine markedly interferes with the metabolism of THD, probably at the CYP2C19 and/or CYP1A2 enzyme level. Therefore, clinicians should be aware of the potential for a clinical drug interaction between both compounds, and careful monitoring of THD levels is valuable to prevent the accumulation of the drug and resulting toxicity.


Assuntos
Antipsicóticos/farmacocinética , Fluvoxamina/farmacocinética , Esquizofrenia/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Tioridazina/farmacocinética , Adulto , Idoso , Antipsicóticos/sangue , Antipsicóticos/uso terapêutico , Citocromo P-450 CYP2D6/genética , Interações Medicamentosas , Fluvoxamina/sangue , Fluvoxamina/uso terapêutico , Humanos , Masculino , Mesoridazina/sangue , Mesoridazina/farmacocinética , Mesoridazina/uso terapêutico , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/sangue , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Tioridazina/sangue , Tioridazina/uso terapêutico
19.
Clin Pharmacol Ther ; 65(4): 369-76, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10223772

RESUMO

The isozymes CYP1A2, CYP2D6, and CYP3A4/5 are involved in the majority of all cytochrome P450-mediated drug biotransformations. In this study we investigated the inhibition profiles of CYP1A2 (substrate: caffeine) CYP2D6 (substrate: dextromethorphan), and CYP3A4/5 (substrate: dextrorphan) by cimetidine, ranitidine, and the novel H2-receptor antagonist ebrotidine in human liver microsomes. The inhibitory effect of the drugs on the enzymes activities were as follows: CYP1A2: cimetidine >> ranitidine = ebrotidine; CYP2D6: cimetidine >>> ranitidine = ebrotidine; CYP3A4/5: ebrotidine > cimetidine >>> ranitidine. The inhibition of CYP3A4/5 enzyme activity by ebrotidine was competitive. To test whether the inhibitory effect of ebrotidine in CYP3A activity was also found in vivo, we analyzed the biodisposition of midazolam in 8 healthy volunteers. Midazolam biodisposition was significantly reduced when administered together with cimetidine (P < .05), whereas no significant inhibition was observed with ebrotidine or ranitidine compared with placebo. Psychomotor performance analysis revealed no significant effect of the observed reduction on midazolam biodisposition. We concluded that patients who are receiving treatment with drugs metabolized through CYP3A may experience enhanced drug effects as a result of pharmacokinetic interaction when treated concomitantly with cimetidine. In contrast, the effect of ranitidine or ebrotidine on CYP3A activity in vivo seems to have little clinical significance.


Assuntos
Ansiolíticos/farmacocinética , Hidrocarboneto de Aril Hidroxilases , Inibidores do Citocromo P-450 CYP1A2 , Inibidores do Citocromo P-450 CYP2D6 , Inibidores das Enzimas do Citocromo P-450 , Antagonistas dos Receptores H2 da Histamina/farmacologia , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Midazolam/farmacocinética , Oxirredutases N-Desmetilantes/antagonistas & inibidores , Adulto , Antitussígenos/farmacocinética , Benzenossulfonatos/farmacologia , Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/farmacocinética , Cimetidina/farmacologia , Citocromo P-450 CYP3A , Dextrometorfano/farmacocinética , Método Duplo-Cego , Humanos , Técnicas In Vitro , Masculino , Metilação/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Ranitidina/farmacologia , Tiazóis/farmacologia
20.
Gac Sanit ; 13(6): 462-7, 1999.
Artigo em Espanhol | MEDLINE | ID: mdl-10620316

RESUMO

OBJECTIVE: Data on meningococcal vaccines safety are scanty. In 1997 several vaccination campaign took place in Spain. Thus, this situation was used to improve our knowledge about the safety profile of this vaccine. METHODS: An inquiry was carried out to the Regional Centers of the Spanish Pharmacovigilance System to know the number of vaccinated people and the type and number of suspected cases of adverse reactions. RESULTS: There were 133 identified cases of suspected adverse reactions associated with meningococcal A and C vaccine until June 1st, 1998. Most of them affected the skin (25,3%) or nervous system (similar proportion). Those of allergic reactions accounted for 35,2%. Two cases were considered as severe, although they were resolved without secuelae. CONCLUSIONS: Serious risks were not detected. The Spanish Pharmacosurveillance System as an epidemiological surveillance resource has been useful to know the safety problems associated with antimeningococcal vaccine in the community.


Assuntos
Vacinas Bacterianas/efeitos adversos , Neisseria meningitidis/imunologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Interpretação Estatística de Dados , Feminino , Humanos , Lactente , Masculino , Vacinas Meningocócicas , Vigilância de Produtos Comercializados , Espanha
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