RESUMEN
1. This study evaluated the minimal inhibitory concentration (MIC) of ciprofloxacin and the presence of plasmid-mediated quinolone resistance (PMQR) mechanisms in 97 nontyphoidal Salmonella spp. isolated from broilers and carcases from three different regions in Brazil. The presence of mutations in quinolone resistance determination regions (QRDRS) was investigated in the ciprofloxacin-resistant strain by DNA sequencing.2. Most of the Salmonella spp. (85.6%) had intermediate resistance to ciprofloxacin and only one isolate was resistant. MIC breakpoints ranged from ≤0.03 to 1 µg/ml and 67.0% of the strains had a MIC of 0.25 µg/ml (n=65). Thirteen strains (13.4%) were susceptible to ciprofloxacin with MIC ≤0.06 µg/ml. The qnrB gene was detected in eight isolates with intermediate resistance and in two susceptible strains. The other PMQR genes, qnrA, qnrC, qnrD, qnrS, qnrVC, aac(6')-Ib, qepA, oqxAB and mutations in QRDR were not detected in any strain.3. There was a high frequency of ciprofloxacin intermediate resistant Salmonella from broiler and broiler carcases from Brazil. The presence of these strains in poultry and derived products poses a risk to public health.
Asunto(s)
Ciprofloxacina , Quinolonas , Animales , Ciprofloxacina/farmacología , Pollos , Brasil , Proteínas Bacterianas/genética , Salmonella , Quinolonas/farmacología , Pruebas de Sensibilidad Microbiana/veterinaria , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genéticaRESUMEN
Cowpea mild mottle virus (CPMMV) is a flexuous filamentous virus that belongs to the genus Carlavirus (family Betaflexiviridae). The CPMMV genome contains six open reading frames (ORFs), among which the triple gene block (TGB), encoded by ORFs 2 to 4, has been reported to encode movement proteins for different viruses. The subcellular localization of the TGB proteins of CPMMV isolate CPMMV:BR:MG:09:2 was analysed by transient expression of each protein fused to a fluorophore. Overall, the accumulation pattern and interactions among CPMMV TGB proteins (TGBp) were similar to those of their counterparts from the potex-like group. Considering these similarities, we evaluated the potential interactions between the TGB proteins of CPMMV and of potato virus X, which could complement cell-to-cell movement. The TGBp2 and TGBp3 of PVX had an effect on CPMMV TGBp1, directing it to the plasmodesmata, but the reverse was not true.
Asunto(s)
Carlavirus , Flexiviridae , Potexvirus , Nicotiana , Proteínas Virales/genética , Proteínas Virales/metabolismo , Carlavirus/genética , Potexvirus/genética , Flexiviridae/genéticaRESUMEN
Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor with a key role in metabolic processes and is target of CDK5 kinase phosphorylation at S245 (S273 in PPARγ isoform 2), thereby inducing insulin resistance. A remarkable effort has been addressed to find PPARγ ligands that inhibit S245 phosphorylation, but the poor understanding in this field challenges the design of such ligands. Here, through computational and biophysical methods, we explored an experimentally validated model of PPARγ-CDK5 complex, and we presented K261, K263 or K265, which are conserved in mammals, as important anchor residues for this interaction. In addition, we observed, from structural data analysis, that PPARγ ligands that inhibit S245 phosphorylation are not in direct contact with these residues; but induce structural modifications in PPARγ:CDK5/p25 interface. In summary, our PPARγ and CDK5/p25 interaction analyses open new possibilities for the rational design of novel inhibitors that impair S245 phosphorylation.
Asunto(s)
Quinasa 5 Dependiente de la Ciclina/química , Complejos Multiproteicos/química , PPAR gamma/química , Conformación Proteica , Animales , Sitios de Unión/genética , Quinasa 5 Dependiente de la Ciclina/genética , Quinasa 5 Dependiente de la Ciclina/metabolismo , Humanos , Ligandos , Modelos Moleculares , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Mutación , PPAR gamma/genética , PPAR gamma/metabolismo , Fosforilación , Unión ProteicaRESUMEN
Coffee ringspot virus (CoRSV) a member of the proposed genus "Dichorhavirus", was surveyed on commercial and research farms spanning an area responsible for the majority of Coffea arabica production in Brazil. Virus-infected plants were found at one hundred percent of locations (n = 45) sampled. All cultivars, regardless of cherry color, were found to serve as hosts, suggesting that there is limited resistance in commercially employed germplasm. Reverse transcription PCR analysis revealed that the virus is contained within symptomatic lesions, with little systemic spread throughout leaves. Phylogenetic analysis based on the ORF1 (nucleocapsid) gene identified a strong geo-spatial relationship among isolates, which clustered into three clades. Despite low genetic diversity among isolates, variation in symptom expression was observed in the experimental host Chenopodium quinoa. Our analyses support the hypothesis that the spread of CoRSV is constrained by the clonal expansion of thelytokous populations of Brevipalpus phoenicis. The widespread occurrence of this virus suggests that it is much more prevalent than previously thought.
Asunto(s)
Coffea/virología , Enfermedades de las Plantas/virología , Virus de Plantas/aislamiento & purificación , Rhabdoviridae/aislamiento & purificación , Animales , Brasil , Análisis por Conglomerados , Variación Genética , Datos de Secuencia Molecular , Filogeografía , Virus de Plantas/clasificación , Virus de Plantas/genética , ARN Viral/análisis , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rhabdoviridae/clasificación , Rhabdoviridae/genética , Análisis de Secuencia de ADN , Homología de SecuenciaRESUMEN
Microsatellite markers have been widely used in the quantification of genetic variability and for genetic breeding in Musa spp. The objective of the present study was to evaluate the discriminatory power of microsatellite markers derived from 'Calcutta 4' and 'Ouro' genomic libraries, and to analyze the genetic variability among 30 banana accessions. Thirty-eight markers were used: 15 from the 'Ouro' library and 23 from the 'Calcutta 4' library. Genetic diversity was evaluated by considering SSR markers as both dominant markers because of the presence of triploid accessions, and co-dominant markers. For the dominant analysis, polymorphism information content (PIC) values for 44 polymorphic markers ranged from 0.063 to 0.533, with a mean value of 0.24. A dendrogram analysis separated the BGB-Banana accessions into 4 groups: the 'Ouro' and 'Muísa Tia' accessions were the most dissimilar (93% dissimilarity), while the most similar accessions were 'Pacovan' and 'Walha'. The mean genetic distance between samples was 0.74. For the analysis considering SSR markers as co-dominants, using only diploid accessions, two groups were separated based on their genome contents (A and B). The PIC values for the markers from the 'Calcutta 4' library varied from 0.4836 to 0.7886, whereas those from the 'Ouro' library ranged from 0.3800 to 0.7521. Given the high PIC values, the markers from both the libraries showed high discriminatory power, and can therefore be widely applied for analysis of genetic diversity, population structures, and linkage mapping in Musa spp.
Asunto(s)
Diploidia , Sitios Genéticos , Genoma de Planta , Biblioteca Genómica , Repeticiones de Microsatélite/genética , Musa/genética , Cartilla de ADN/genética , Electroforesis en Gel de Agar , Marcadores Genéticos , Variación Genética , Genotipo , FilogeniaRESUMEN
Red-fleshed oranges (Citrus sinensis) contain high levels of carotenoids and lycopene. The growing consumer demand for products with health benefits has increased interest in these types of Citrus cultivars as a potential source of nutraceuticals. However, little is known about the physiology of these cultivars under Brazilian conditions. Transcriptome and gene expression analyses are important tools in the breeding and management of red-fleshed sweet orange cultivars. Reverse transcription quantitative polymerase chain reaction is a method of quantifying gene expression, but various standardizations are required to obtain precise, accurate, and specific results. Among the standardizations required, the choice of suitable stable reference genes is fundamental. The objective of this study was to evaluate the stability of 11 candidate genes using various tissue and organ samples from healthy plants or leaves from citrus greening disease (Huanglongbing)-symptomatic plants of a Brazilian red-fleshed cultivar ('Sanguínea de Mombuca'), in order to select the most suitable reference gene for investigating gene expression under these conditions. geNorm and NormFinder identified genes that encoded translation initiation factor 3, ribosomal protein L35, and translation initiation factor 5A as the most stable genes under the biological conditions tested, and genes coding actin (ACT) and the subunit of the PSI reaction center subunit III were the least stable. Phosphatase, malate dehydrogenase, and ACT were the most stable genes in the leaf samples of infected plants.
Asunto(s)
Citrus sinensis/genética , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Transcriptoma , Biología Computacional/métodos , Variación GenéticaRESUMEN
Brown rust (causal agent Puccinia melanocephala) is an important sugarcane disease that is responsible for large losses in yield worldwide. Despite its importance, little is known regarding the genetic diversity of this pathogen in the main Brazilian sugarcane cultivation areas. In this study, we characterized the genetic diversity of 34 P. melanocephala isolates from 4 Brazilian states using loci identified from an enriched simple sequence repeat (SSR) library. The aggressiveness of 3 isolates from major sugarcane cultivation areas was evaluated by inoculating an intermediately resistant and a susceptible cultivar. From the enriched library, 16 SSR-specific primers were developed, which produced scorable alleles. Of these, 4 loci were polymorphic and 12 were monomorphic for all isolates evaluated. The molecular characterization of the 34 isolates of P. melanocephala conducted using 16 SSR loci revealed the existence of low genetic variability among the isolates. The average estimated genetic distance was 0.12. Phenetic analysis based on Nei's genetic distance clustered the isolates into 2 major groups. Groups I and II included 18 and 14 isolates, respectively, and both groups contained isolates from all 4 geographic regions studied. Two isolates did not cluster with these groups. It was not possible to obtain clusters according to location or state of origin. Analysis of disease severity data revealed that the isolates did not show significant differences in aggressiveness between regions.
Asunto(s)
Basidiomycota/genética , Variación Genética , Repeticiones de Microsatélite , Secuencia de Bases , Basidiomycota/clasificación , Brasil , Cartilla de ADN , Marcadores GenéticosRESUMEN
Fig (Ficus carica) breeding programs that use conventional approaches to develop new cultivars are rare, owing to limited genetic variability and the difficulty in obtaining plants via gamete fusion. Cytosine methylation in plants leads to gene repression, thereby affecting transcription without changing the DNA sequence. Previous studies using random amplification of polymorphic DNA and amplified fragment length polymorphism markers revealed no polymorphisms among select fig mutants that originated from gamma-irradiated buds. Therefore, we conducted methylation-sensitive amplified polymorphism analysis to verify the existence of variability due to epigenetic DNA methylation among these mutant selections compared to the main cultivar 'Roxo-de-Valinhos'. Samples of genomic DNA were double-digested with either HpaII (methylation sensitive) or MspI (methylation insensitive) and with EcoRI. Fourteen primer combinations were tested, and on an average, non-methylated CCGG, symmetrically methylated CmCGG, and hemimethylated hmCCGG sites accounted for 87.9, 10.1, and 2.0%, respectively. MSAP analysis was effective in detecting differentially methylated sites in the genomic DNA of fig mutants, and methylation may be responsible for the phenotypic variation between treatments. Further analyses such as polymorphic DNA sequencing are necessary to validate these differences, standardize the regions of methylation, and analyze reads using bioinformatic tools.
Asunto(s)
Metilación de ADN , Ficus/genética , Mutación , Polimorfismo Genético , FenotipoRESUMEN
Obesity is one of the main risk factors for type 2 diabetes, and peroxisome proliferator-activated receptor γ (PPARγ) is considered a promising pathway on insulin sensitivity and adipose tissue metabolism. The search for molecules acting as insulin sensitizers have increased, especially for molecules that block PPARγ-Ser273 phosphorylation, without reaching full agonism. We evaluated the in vivo effects of AM-879, a PPARγ non-agonist, and found that AM-879 exerts different effects in mice depending on the dose. At lower doses, this ligand decreased BAT, increased leptin and Crh expression. However, at a higher dose, it promoted improvement on insulin sensitivity, ameliorates expression of metabolism-related genes, decreased the expression of genes related to liver toxicity, maintaining body weight and adipocyte size. These results present a new lead molecule to ameliorates insulin resistance and confirm AM-879 as a PPARγ non-agonist which blocks Ser273 phosphorylation as a good strategy to modulate insulin sensitivity without developing the adverse effects promoted by PPARγ full agonists.
RESUMEN
Understanding the mating patterns of populations of tree species is a key component of ex situ genetic conservation. In this study, we analysed the genetic diversity, spatial genetic structure (SGS) and mating system at the hierarchical levels of fruits and individuals as well as pollen dispersal patterns in a continuous population of Theobroma cacao in Pará State, Brazil. A total of 156 individuals in a 0.56 ha plot were mapped and genotyped for nine microsatellite loci. For the mating system analyses, 50 seeds were collected from nine seed trees by sampling five fruits per tree (10 seeds per fruit). Among the 156 individuals, 127 had unique multilocus genotypes, and the remaining were clones. The population was spatially aggregated; it demonstrated a significant SGS up to 15 m that could be attributed primarily to the presence of clones. However, the short seed dispersal distance also contributed to this pattern. Population matings occurred mainly via outcrossing, but selfing was observed in some seed trees, which indicated the presence of individual variation for self-incompatibility. The matings were also correlated, especially within (Ρ(p(m))=0.607) rather than among the fruits (Ρ(p(m))=0.099), which suggested that a small number of pollen donors fertilised each fruit. The paternity analysis suggested a high proportion of pollen migration (61.3%), although within the plot, most of the pollen dispersal encompassed short distances (28 m). The determination of these novel parameters provides the fundamental information required to establish long-term ex situ conservation strategies for this important tropical species.
Asunto(s)
Cacao/genética , Frutas/genética , Variación Genética/genética , Brasil , Flujo Génico/genética , Genética de Población , Genotipo , Repeticiones de Microsatélite/genética , Polen/genética , Polinización/genética , Reproducción/genéticaRESUMEN
Lack of continuous progress in Theobroma cacao (Malvaceae) breeding, especially associated with seed quality traits, requires more efficient selection methods based on genomic information. Reverse transcript quantitative PCR (RT-qPCR) has become the method of choice for gene expression analysis, but relative expression analysis requires various reference genes, which must be stable across various biological conditions. We sought suitable reference genes for various tissues of cacao, especially developing seeds. Ten potential reference genes were analyzed for stability at various stages of embryo development, leaves, stems, roots, flowers, and pod epicarp; seven of them were also evaluated in shoot tips treated either with hormones (salicylate; ethefon; methyl-jasmonate) or after inoculation with the fungus Moniliophthora perniciosa (Marasmiaceae sensu lato). For developing embryos, the three most stable genes were actin (ACT), polyubiquitin (PUB), and ribosomal protein L35 (Rpl35). In the analyses of various tissues, the most stable genes were malate dehydrogenase (MDH), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and acyl-carrier protein B (ACP B). GAPDH, MDH and tubulin (TUB) were the most appropriate for normalization when shoot apexes were treated with hormones, while ACT, TUB and Rpl35 were the most appropriate after inoculation with M. perniciosa. We conclude that for each plant system and biological or ontogenetical condition, there is a need to define suitable reference genes. This is the first report to define reference genes for expression studies in cacao.
Asunto(s)
Cacao/genética , Regulación de la Expresión Génica de las Plantas , Especificidad de Órganos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , Perfilación de la Expresión Génica , Genes de Plantas/genética , Estudios de Asociación Genética , Estándares de Referencia , Programas InformáticosRESUMEN
The effect of ultrasound on the crystal size, phenols, flavonoids, Maillard products and antibacterial activity of crystallized honeys was studied. Three multifloral honeys (M), one monofloral (MO) and one honeydew (HD) honey were used. Ultrasound was performed at 42 kHz for different times (0, 5, 10 and 15 min). The antibacterial activities were tested against Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Listeria monocytogenes, Staphylococcus aureus and Escherichia coli. In all honeys, the parameters analyzed had significant differences ((P < 0.05)). After 15 min of ultrasound the HD had increments of 44 mg of gallic acid/100 g of honey in phenols, and some M showed increase in flavonoids (5.64 mg of quercitin /100 g of honey) and improvement in inhibition against Salmonella typhimurium was 13.1%. In some honeys the correlation between phenols or flavonoids and antibacterial activity were significant ((P < 0.05)). No correlation was found between Maillard products and antibacterial activity. The ultrasound treatment effect on the crystal size, phenols, flavonoid, Maillard products, and antibacterial activity of crystallized honeys were different in each honey.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Miel , Ondas Ultrasónicas , Cerámica , Flavonoides/química , Vidrio , Fenoles/químicaRESUMEN
In this work, the effect of a solid fungal culture of Aspergillus niger (An) grown on coffee pulp on the in situ ruminal degradability (RD) of corn stover was evaluated. In addition, the effect of its extracts on the in vitro dry matter disappearance (IVDMD) and on a mixed culture of anaerobic cellulolytic bacteria (MCACB) was also investigated. The solid ferment was a crude culture of An, grown on coffee pulp. Regarding in situ RD, a significant difference (p < 0.05) was found between treatment with 200 g/day of the solid culture and control (no solid culture added) on dry matter, crude protein and neutral detergent fibre on RD. All the water extracts (pH 4, 7 and 10) enhanced IVDMD and stimulated the cellulolytic activity on a MCACB. Ultrafiltration results showed that active compounds with a molecular weight lower than 30 kDa were responsible for the effect on MCACB. Such results suggest that the effects of the solid An culture in RD are related to the presence of water soluble compounds having a molecular weight lower than 30 kDa.
Asunto(s)
Aspergillus niger/fisiología , Bacterias Anaerobias/fisiología , Bovinos/fisiología , Celulosa/metabolismo , Rumen/fisiología , Aerobiosis , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Digestión , Femenino , Zea maysRESUMEN
Productivity of 'yellow' passion fruit (Passiflora edulis Sims. f. flavicarpa O. Deg.) is reduced by infection with Cowpea aphid-borne mosaic virus (CABMV). We examined resistance in 72 yellow passion fruit plants grown from open-pollinated commercial seed. Plants were mechanically inoculated with CABMV virus and maintained in the field in order to select contrasting genotypes for resistance. Isolates were obtained from symptomatic leaves of yellow passion fruit plants from field production in Livramento de Nossa Senhora, Bahia state and were characterized by sequencing the viral coat protein gene. Severity of leaf symptoms of the disease, evaluated through a global leaf disease index, was measured during the eighth month of growth. Morpho-agronomic variables of fruit were evaluated from months 10 to 12. Significant linear regressions between the quantification of the leaf symptoms and the morpho-agronomic characteristics related to productivity were detected (5.17% Asunto(s)
Comovirus/patogenicidad
, Passiflora/genética
, Passiflora/virología
, Enfermedades de las Plantas/genética
, Enfermedades de las Plantas/virología
, Brasil
, Comovirus/genética
, Predisposición Genética a la Enfermedad/genética
, Passiflora/crecimiento & desarrollo
, Hojas de la Planta/virología
RESUMEN
AIM: Exercise training has been suggested as a non-pharmacological approach to prevent skeletal muscle wasting and improve muscle function in cancer cachexia. However, little is known about the molecular mechanisms underlying such beneficial effect. In this study, we aimed to, firstly, examine the contribution of TWEAK signalling to cancer-induced skeletal muscle wasting and, secondly, evaluate whether long-term exercise alters TWEAK signalling and prevents muscle wasting. METHODS: Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Fifteen animals from each group were exposed to N-Methyl-N-nitrosourea carcinogen. Animals in exercise groups were submitted to moderate treadmill exercise for 35 weeks. After the experimental period, animals were killed and gastrocnemius muscles were harvested for morphological and biochemical analysis. RESULTS: We verified that exercise training prevented tumour-induced TWEAK/NF-κB signalling in skeletal muscle with a beneficial impact in fibre cross-sectional area and metabolism. Indeed, 35 weeks of exercise training promoted the upregulation of PGC-1α and oxidative phosphorylation complexes. This exercise-induced muscle remodelling in tumour-bearing animals was associated with less malignant mammary lesions. CONCLUSION: Data support the benefits of an active lifestyle for the prevention of muscle wasting secondary to breast cancer, highlighting TWEAK/NF- κB signalling as a potential therapeutic target for the preservation of muscle mass.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/biosíntesis , Caquexia/metabolismo , Neoplasias Mamarias Experimentales/complicaciones , Proteínas de la Membrana/biosíntesis , Condicionamiento Físico Animal/métodos , Transducción de Señal , Factores de Necrosis Tumoral/biosíntesis , Animales , Caquexia/etiología , Citocina TWEAK , Modelos Animales de Enfermedad , Femenino , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/etiología , Atrofia Muscular/metabolismo , FN-kappa B/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiologíaRESUMEN
O objetivo deste trabalho foi estudar a prevalência de MG e MS e a filogenia das cepas circulantes, comparando-as com outras já descritas em poedeiras comerciais no Brasil. Foram coletados 140 suabes traqueais de poedeiras comerciais com sinais respiratórios em seis granjas da região centro-oeste de São Paulo. As amostras foram avaliadas por PCR, com posterior sequenciamento e análise filogenética das cepas identificadas. Das 140 amostras, 16,4% foram positivas para MG e 68,6% para MS. Houve diferença significativa nas frequências de MG e MS por granja, segundo o teste G de independência (P<0,05). Todas as cepas identificadas de MG e MS de granjas distintas apresentaram similaridade tanto pela lipoproteína para MG quanto pela região 16s rRNA para MS. Neste estudo, foi possível observar altas prevalências dos agentes estudados, sendo a de MS maior que a de MG. Foi detectada infecção mista por MG e MS em 11,4% das amostras e sabe-se que esses micoplasmas podem agir de forma sinérgica, agravando o quadro respiratório. As cepas circulantes identificadas, pela análise das regiões gênicas da lipoproteína para MG e 16S rRNA para MS, são similares em todas as granjas estudadas.(AU)
The aim of this study was to evaluate the prevalence of MG and MS and the phylogeny of the circulating strains, comparing them with others already described in commercial laying hens from Brazil. A total of 140 tracheal swabs were collected from commercial laying hens with respiratory signs in six farms from the western region of São Paulo state. The samples were analyzed by PCR with subsequent sequencing and phylogenetic analysis of the identified strains. From the 140 samples, 68.6% were positive for MS and 16.4% for MG. There was a significant difference in the frequencies of MG and MS per farm according to G Test of independence (P<0.05). All strains identified as MG and MS from distinct farms presented similarity both by lipoprotein to MG and by 16s rRNA region to MS. In this study, it was possible to observe a high prevalence of MS compared to MG. Mixed MG and MS infection was detected in 11.4% of the samples. These mycoplasmas may act synergistically, worsening the respiratory signs. The circulating strains identified by analysis of the lipoprotein for MG and 16S rRNA for MS are similar on all poultry farms studied.(AU)
Asunto(s)
Animales , Filogenia , Aves de Corral , Pollos/microbiología , Mycoplasma gallisepticum , Mycoplasma synoviae , Estudios TransversalesAsunto(s)
Personajes , Biología Marina/historia , Historia del Siglo XIX , Historia del Siglo XX , PortugalRESUMEN
PURPOSE: The combination of bolus doxorubicin followed by a 3-h infusion of paclitaxel has high antitumor activity in patients with metastatic breast cancer, but is limited by unexpected cardiac toxicity. In contrast, the administration of the two drugs 16 h apart has similar antitumor activity but less cardiac toxicity. The purpose of this study was to compare the pharmacokinetics of these drugs when doxorubicin administration preceded paclitaxel by 30 min or by 24 h. PATIENTS AND METHODS: Women with locally advanced breast cancer were treated with doxorubicin (60 mg/m2 i.v. bolus) followed 24 h later by paclitaxel (200 mg/m2 i.v. over 3 h) for six cycles (four before and two after surgery). In one of the first two cycles doxorubicin preceded paclitaxel by 30 min instead of 24 h, with plasma sampling for pharmacokinetic analysis up to 48 h. Determination of drug levels in plasma was done by HPLC. RESULTS: A total of 28 patients were included. No clinical cardiac toxicity was observed but five patients discontinued doxorubicin-paclitaxel treatment after four cycles because of a decrease in LVEF of at least 15% from baseline or to less than 50%. While paclitaxel pharmacokinetics were not changed, there was a 30% and an 80% increase in the AUC0, 24h for doxorubicin and doxorubicinol, respectively, when the drugs were administered 30 min instead of 24 h apart. Even when paclitaxel was given 24 h after doxorubicin, there was a rebound 240% increase in the plasma concentration of doxorubicinol. CONCLUSIONS: Paclitaxel interferes with the pharmacokinetics of doxorubicin leading to higher systemic exposure to both doxorubicin and doxorubicinol, which is more evident when the plasma concentration of the anthracyclines is higher. This interference may explain the higher incidence of cardiac toxicity observed when the two drugs are administered within a short interval.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/efectos adversos , Doxorrubicina/farmacocinética , Paclitaxel/administración & dosificación , Paclitaxel/farmacocinética , Adulto , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Área Bajo la Curva , Doxorrubicina/administración & dosificación , Esquema de Medicación , Interacciones Farmacológicas , Femenino , Corazón/efectos de los fármacos , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Persona de Mediana Edad , Paclitaxel/efectos adversos , Volumen SistólicoRESUMEN
The authors present 69 patients with duodenal ulcer considered as non-resectable ("difficult duodenum"). Troncular vagotomy associated with gastrojejunostomy (VTGE) were performed in 26 cases. This surgical approach was chosen for patients with advanced age, poor general condition and, obesity. When local conditions such as deformity, post-bulbar ulcer and penetrating ulcers were present, troncular vagotomy with antrectomy and Finsterer exclusion (VTAF) was the procedure of choice (43 cases). The incidence of duodenal fistula during the hospital stay was high (6,9%) in the VTAF group but the mortality rate was low, as oposed to the high mortality rate after VTGE. This is in agreement with other authors. Regarding the late results (follow-up for over 1 year in 58.3% of the VTGE group and, 70.5% of the VTAF group) a recurrence rate of 16.6% was observed in the VTGE group and, none in the CTAF group. The authors conclude that in the non-resectable duodenum, the procedure of choice is troncular vagotomy with antrectomy and Finsterer exclusion. Troncular vagotomy and jejunostomy should be considered as an alternative and, performed only in obese patients, over the age of 65 and in poor general condition.