RESUMO
Gallstones Disease (GSD) is one of the most common digestive diseases requiring hospitalization and surgical procedures in the world. GSD has a high prevalence in populations with European or Amerindian ancestry (10-20%) and the influence of genetic factors is broadly acknowledged. However, known genetic variants do not entirely explain the disease heritability suggesting that additional genetic variants remain to be identified. Here, we examined the association of copy number variants (CNVs) with GSD in a sample of 4778 individuals (1929 GSD cases and 2849 controls) including two European cohorts from Germany (n = 3702) and one admixed Latin American cohort from Chile (n = 1076). We detected 2936 large and rare CNVs events (size > 100 kb, frequency < 1%). Case-control burden analysis and generalized linear regression models revealed significant association of CNVs with GSD in men, with the strongest effect observed with CNVs overlapping lipid metabolism genes (p-value = 6.54 × 10-4; OR = 2.76; CI 95% = 1.53-4.89). Our results indicate a clear link between CNVs and GSD in men and provides additional evidence that the genetic components of risk for GSD are complex, can be sex specific and include CNVs affecting genes involved in lipid metabolism.
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Variações do Número de Cópias de DNA , Cálculos Biliares/genética , Metabolismo dos Lipídeos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
Whole human genome sequencing initiatives help us understand population history and the basis of genetic diseases. Current data mostly focuses on Old World populations, and the information of the genomic structure of Native Americans, especially those from the Southern Cone is scant. Here we present annotation and variant discovery from high-quality complete genome sequences of a cohort of 11 Mapuche-Huilliche individuals (HUI) from Southern Chile. We found approximately 3.1 × 106 single nucleotide variants (SNVs) per individual and identified 403,383 (6.9%) of novel SNVs events. Analyses of large-scale genomic events detected 680 copy number variants (CNVs) and 4,514 structural variants (SVs), including 398 and 1,910 novel events, respectively. Global ancestry composition of HUI genomes revealed that the cohort represents a sample from a marginally admixed population from the Southern Cone, whose main genetic component derives from Native American ancestors. Additionally, we found that HUI genomes contain variants in genes associated with 5 of the 6 leading causes of noncommunicable diseases in Chile, which may have an impact on the risk of prevalent diseases in Chilean and Amerindian populations. Our data represents a useful resource that can contribute to population-based studies and for the design of early diagnostics or prevention tools for Native and admixed Latin American populations.
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Etnicidade/genética , Marcadores Genéticos , Genética Populacional , Genoma Humano , Genômica/métodos , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Genoma/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Chile , Estudos de Coortes , Variações do Número de Cópias de DNA , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10-5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10-8, OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10-7, OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.
Assuntos
Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Neoplasias da Vesícula Biliar/etiologia , Cálculos Biliares/genética , Indígenas Sul-Americanos/genética , Polimorfismo de Nucleotídeo Único , Fator 3 Associado a Receptor de TNF/genética , População Branca/genética , Adulto , Idoso , Chile/etnologia , Colecistectomia , Regulação para Baixo , Duodeno/química , Feminino , Vesícula Biliar/química , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/etnologia , Neoplasias da Vesícula Biliar/cirurgia , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/etnologia , Cálculos Biliares/cirurgia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
PURPOSE: To determine the efficacious cefazolin prophylactic dose for bariatric surgery using free subcutaneous concentrations accessed by microdialysis after 2 g or 3 g i.v. bolus dosing to morbidly obese women and POPPK modeling. METHODS: A POPPK model with variable plasma and subcutaneous tissue protein binding was developed to simultaneously describe plasma and tissue data sets. The outcomes was predicted for common surgical site infection (SSI) bacteria over 3, 4, 5 and 6 h periods postdose, as probability of target attainment (PTA) using Monte Carlo simulation. RESULTS: CFZ 2 g warrant up to 5 h SSI prophylaxis for bacteria with MICs ≤1 mg/L such as Escherichia coli and Staphylococcus aureus. For species such as Klebsiella pneumoniae, which present MIC distribution frequency of 2 mg/L, the maintenance of PTA ≥ 90% occurs with a 3 g dose for surgeries lasting up to 5 h, and 2 g dose provide an adequate response up to 4 h (PTA of 89%). CONCLUSIONS: Effectiveness of CFZ 2 g is similar to 3 g against bacteria with a MIC up to 2 mg/L, especially if the surgery does not last for more than 4 h.
Assuntos
Antibioticoprofilaxia/métodos , Cirurgia Bariátrica/efeitos adversos , Cefazolina/administração & dosagem , Modelos Biológicos , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Cirurgia Bariátrica/métodos , Cefazolina/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Testes de Sensibilidade Microbiana , Microdiálise , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Tela Subcutânea/metabolismo , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/microbiologia , Adulto JovemRESUMO
Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals owing to alterations in drug tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need for cefazolin prophylactic dose adjustment in obese patients remains under discussion. The paper describes the validation of an HPLC-UV method for cefazolin quantification in plasma and microdialysate samples from clinical and pre-clinical studies. A C18 column with an isocratic mobile phase was used for drug separation, with detection at 272 nm. Total and unbound cefazolin lower limit of quantitation was 5 µg/mL in human plasma, 2 µg/mL in rat plasma, and 0.5 and 0.025 µg/mL in human and rat microdialysate samples, respectively. The maximum intra- and inter-day imprecisions were 10.7 and 8.1%, respectively. The inaccuracy was <9.7%. The limit of quantitation imprecision and inaccuracy were < 15%. Cefazolin stability in the experimental conditions was confirmed. Cefazolin plasma concentrations and subcutaneous tissue penetration were determined by microdialysis in morbidly obese patients (2 g i.v. bolus) and diet-induced obese rats (30 mg/kg i.v. bolus) using the method. This method has the main advantages of easy plasma clean-up and practicability and has proven to be useful in cefazolin clinical and pre-clinical pharmacokinetic investigations.
Assuntos
Cefazolina/sangue , Cefazolina/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Obesidade/metabolismo , Espectrofotometria Ultravioleta/métodos , Adolescente , Adulto , Animais , Cefazolina/química , Estabilidade de Medicamentos , Humanos , Modelos Lineares , Masculino , Microdiálise , Pessoa de Meia-Idade , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tela Subcutânea/química , Adulto JovemRESUMO
BACKGROUND: Fragmentation of native forests is a highly visible result of human land-use throughout the world. In this study, we evaluated the effects of landscape fragmentation and matrix features on the genetic diversity and structure of Oligoryzomys longicaudatus, the natural reservoir of Hantavirus in southern South America. We focused our work in the Valdivian Rainforest where human activities have produced strong change of natural habitats, with an important number of human cases of Hantavirus. METHODS: We sampled specimens of O. longicaudatus from five native forest patches surrounded by silvoagropecuary matrix from Panguipulli, Los Rios Region, Chile. Using the hypervariable domain I (mtDNA), we characterized the genetic diversity and evaluated the effect of fragmentation and landscape matrix on the genetic structure of O. longicaudatus. For the latter, we used three approaches: (i) Isolation by Distance (IBD) as null model, (ii) Least-cost Path (LCP) where genetic distances between patch pairs increase with cost-weighted distances, and (iii) Isolation by Resistance (IBR) where the resistance distance is the average number of steps that is needed to commute between the patches during a random walk. RESULTS: We found low values of nucleotide diversity (π) for the five patches surveyed, ranging from 0.012 to 0.015, revealing that the 73 sampled specimens of this study belong to two populations but with low values of genetic distance (γST ) ranging from 0.022 to 0.099. Likewise, we found that there are no significant associations between genetic distance and geographic distance for IBD and IBR. However, we found for the LCP approach, a significant positive relationship (r = 0.737, p = 0.05), with shortest least-cost paths traced through native forest and arborescent shrublands. DISCUSSION: In this work we found that, at this reduced geographical scale, Oligoryzomys longicaudatus shows genetic signs of fragmentation. In addition, we found that connectivity between full growth native forest remnants is mediated by the presence of dense shrublands and native forest corridors. In this sense, our results are important because they show how native forest patches and associated routes act as source of vector species in silvoagropecuary landscape, increasing the infection risk on human population. This study is the first approach to understand the epidemiological spatial context of silvoagropecuary risk of Hantavirus emergence. Further studies are needed to elucidate the effects of landscape fragmentation in order to generate new predictive models based on vector intrinsic attributes and landscape features.
RESUMO
BACKGROUND: Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement 'hotspot' loci. However, microdeletion burden not overlapping these regions or within different epilepsy subtypes has not been ascertained. OBJECTIVE: To decipher the role of microdeletions outside hotspots loci and risk assessment by epilepsy subtype. METHODS: We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1366 patients with genetic generalised epilepsy (GGE) in addition to two sets of additional unpublished genome-wide microdeletions found in 281 patients with rolandic epilepsy (RE) and 807 patients with adult focal epilepsy (AFE), totalling 2454 cases. Microdeletions were assessed in a combined and subtype-specific approaches against 6746 controls. RESULTS: When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted p=1.06×10-6,OR 1.89, 95% CI 1.51 to 2.35). Epilepsy subtype-specific analyses showed that hotspot microdeletions in the GGE subgroup contribute most of the overall signal (adjusted p=9.79×10-12, OR 7.45, 95% CI 4.20-13.5). Outside hotspots , microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted p=9.13×10-3,OR 2.85, 95% CI 1.62-4.94). No additional signal was observed for RE and AFE. Still, gene-content analysis identified known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes across epilepsy subtypes that were not deleted in controls. CONCLUSIONS: Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor contribution in the aetiology of RE and AFE.
Assuntos
Deleção Cromossômica , Epilepsias Parciais/genética , Epilepsia Generalizada/genética , Epilepsia Rolândica/genética , Estudos de Casos e Controles , Estudos de Coortes , Variações do Número de Cópias de DNA , Expressão Gênica , Estudos de Associação Genética , HumanosRESUMO
Wnt/ß-catenin signaling modulates brain development and function and its deregulation underlies pathological changes occurring in neurodegenerative and neurodevelopmental disorders. Since one of the main effects of Wnt/ß-catenin signaling is the modulation of target genes, in the present work we examined global transcriptional changes induced by short-term Wnt3a treatment (4 h) in primary cultures of rat hippocampal neurons. RNAseq experiments allowed the identification of 170 differentially expressed genes, including known Wnt/ß-catenin target genes such as Notum, Axin2, and Lef1, as well as novel potential candidates Fam84a, Stk32a, and Itga9. Main biological processes enriched with differentially expressed genes included neural precursor (GO:0061364, p-adjusted = 2.5 × 10-7), forebrain development (GO:0030900, p-adjusted = 7.3 × 10-7), and stem cell differentiation (GO:0048863 p-adjusted = 7.3 × 10-7). Likewise, following activation of the signaling cascade, the expression of a significant number of genes with transcription factor activity (GO:0043565, p-adjusted = 4.1 × 10-6) was induced. We also studied molecular networks enriched upon Wnt3a activation and detected three highly significant expression modules involved in glycerolipid metabolic process (GO:0046486, p-adjusted = 4.5 × 10-19), learning or memory (GO:0007611, p-adjusted = 4.0 × 10-5), and neurotransmitter secretion (GO:0007269, p-adjusted = 5.3 × 10-12). Our results indicate that Wnt/ß-catenin mediated transcription controls multiple biological processes related to neuronal structure and activity that are affected in synaptic dysfunction disorders.
Assuntos
Hipocampo/fisiologia , Neurônios/fisiologia , Transcrição Gênica/fisiologia , Via de Sinalização Wnt/fisiologia , beta Catenina/fisiologia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Feminino , Redes Reguladoras de Genes/fisiologia , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
MOTIVATION: Boolean networks (BNs) are commonly used to model genetic regulatory networks (GRNs). Due to the sensibility of the dynamical behavior to changes in the updating scheme (order in which the nodes of a network update their state values), it is increasingly common to use different updating rules in the modeling of GRNs to better capture an observed biological phenomenon and thus to obtain more realistic models.In Aracena et al. equivalence classes of deterministic update schedules in BNs, that yield exactly the same dynamical behavior of the network, were defined according to a certain label function on the arcs of the interaction digraph defined for each scheme. Thus, the interaction digraph so labeled (update digraphs) encode the non-equivalent schemes. RESULTS: We address the problem of enumerating all non-equivalent deterministic update schedules of a given BN. First, we show that it is an intractable problem in general. To solve it, we first construct an algorithm that determines the set of update digraphs of a BN. For that, we use divide and conquer methodology based on the structural characteristics of the interaction digraph. Next, for each update digraph we determine a scheme associated. This algorithm also works in the case where there is a partial knowledge about the relative order of the updating of the states of the nodes. We exhibit some examples of how the algorithm works on some GRNs published in the literature. AVAILABILITY AND IMPLEMENTATION: An executable file of the UpdateLabel algorithm made in Java and the files with the outputs of the algorithms used with the GRNs are available at: www.inf.udec.cl/ â¼lilian/UDE/ CONTACT: lilisalinas@udec.cl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Redes Reguladoras de Genes , Algoritmos , Modelos TeóricosRESUMO
Genome-wide association studies (GWAS) have successfully identified several risk loci for Alzheimer's disease (AD). Nonetheless, these loci do not explain the entire susceptibility of the disease, suggesting that other genetic contributions remain to be identified. Here, we performed a meta-analysis combining data of 4,569 individuals (2,540 cases and 2,029 healthy controls) derived from three publicly available GWAS in AD and replicated a broad genomic region (>248,000 bp) associated with the disease near the APOE/TOMM40 locus in chromosome 19. To detect minor effect size contributions that could help to explain the remaining genetic risk, we conducted network-based pathway analyses either by extracting gene-wise p-values (GW), defined as the single strongest association signal within a gene, or calculated a more stringent gene-based association p-value using the extended Simes (GATES) procedure. Comparison of these strategies revealed that ontological sub-networks (SNs) involved in glutamate signaling were significantly overrepresented in AD (p<2.7×10(-11), p<1.9×10(-11); GW and GATES, respectively). Notably, glutamate signaling SNs were also found to be significantly overrepresented (p<5.1×10(-8)) in the Alzheimer's disease Neuroimaging Initiative (ADNI) study, which was used as a targeted replication sample. Interestingly, components of the glutamate signaling SNs are coordinately expressed in disease-related tissues, which are tightly related to known pathological hallmarks of AD. Our findings suggest that genetic variation within glutamate signaling contributes to the remaining genetic risk of AD and support the notion that functional biological networks should be targeted in future therapies aimed to prevent or treat this devastating neurological disorder.
Assuntos
Doença de Alzheimer/genética , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Glutamatos/metabolismo , Transdução de Sinais/genética , Encéfalo/metabolismo , Encéfalo/patologia , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Neuroimagem , Reprodutibilidade dos Testes , Sinapses/metabolismoRESUMO
We previously found that single nucleotide polymorphisms in the low-density lipoprotein receptor-related protein 6 (LRP6) gene are associated with Alzheimer's disease (AD). Here, we studied the posttranscriptional metabolism of the LRP6 message scanning sequentially the 23 LRP6 exons in human tissues and found a novel LRP6 isoform that completely skips exon 3 (LRP6Δ3) in all tissues examined and was also conserved in mice. Expression levels of the LRP6 isoforms were determined in 47 cortical brain messenger (m)RNA samples including 22 AD cases, 11 control subjects, and 14 individuals with other neurological disorders. LRP6Δ3 mRNA levels were significantly augmented in AD brains compared with controls (1.6-fold; p = 0.037) or other pathological samples (2-fold; p = 0.007). Functional analysis in Wnt/ß-catenin signaling assays revealed that skipping of exon 3 reduced significantly the signaling activity of the LRP6 coreceptor. We conclude that the LRP6Δ3 isoform is a novel splice variant, which shows diminished Wnt/ß-catenin signaling activity and might have a functional role in individuals with AD.
Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Estudos de Associação Genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Isoformas de Proteínas/genética , Via de Sinalização Wnt/genética , Idoso , Idoso de 80 Anos ou mais , Processamento Alternativo/genética , Animais , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Pessoa de Meia-IdadeRESUMO
A modified E(max)-pharmacokinetic-pharmacodynamic (PK-PD) model was previously proposed in literature for describing the antimicrobial activity of ß-lactam antibiotics based on in vitro experiments. However, bacteria behave differently in vitro and in vivo. Thus, the aims of this study were to model the killing effect of piperacillin (PIP) against Escherichia coli on immunocompromised infected rats using this model and to compare the parameters obtained in vitro and in vivo for the same bacteria/drug combination. The PK-PD parameters determined in vitro and in vivo were as follows: generation rate constant of 1.30 ± 0.10 and 0.76 ± 0.20 h(-1), maximum killing effect of 3.11 ± 0.27 and 1.38 ± 0.20 h(-1) and concentration to produce 50% of the maximum effect of 5.44 ± 0.03 and 1.31 ± 0.27 µg ml(-1), respectively. The comparison between the in vitro and in vivo parameters was not straightforward and had to take into consideration the intrinsic differences of the models involved. So far, the main application of the PK-PD model evaluated is for the comparison of different antimicrobial agent's potency and efficacy, under equivalent conditions.
Assuntos
Antibacterianos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Modelos Biológicos , Piperacilina/farmacologia , Animais , Antibacterianos/farmacocinética , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Masculino , Piperacilina/farmacocinética , Ratos , Ratos Wistar , beta-Lactamas/farmacocinética , beta-Lactamas/farmacologiaRESUMO
A rapid, sensitive, and simple HPLC/MS/MS method was developed and validated for the determination of (5Z,E)-3-[2-(4-chlorophenyl)-2-oxoethyl]-5-(1H-indol-3-ylmethylene)-thiazolidine-2, 4-dione (PG15) in rat plasma using chlortalidone as an internal standard (IS). Analyses were performed using a C18 column and isocratic elution with acetonitrile-water (90 + 10, v/v) containing 10 mM ammonium hydroxide (pH 8.0) as the mobile phase pumped at 0.3 mL/min. Detection was performed by MS with negative ion mode electrospray ionization. Rat plasma samples were prepared by deproteinizing with acetonitrile. Detected fragments were 395.1 > 171.9 for PG15 and 337.3 > 189.9 for the IS. Calibration curves were linear from 10 to 1000 ng/mL, with the determination coefficient > 0.99. The intraday and interday precisions were less than 12.2 and 11.3%, respectively. The applicability of the HPLC/MS/MS method for pharmacokinetic studies was tested using plasma samples obtained after oral administration of PG15 to rats, and it provided the necessary sensitivity, linearity, precision, accuracy, and specificity.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Indóis/sangue , Espectrometria de Massas em Tandem/métodos , Tiazolidinas/sangue , Animais , Estabilidade de Medicamentos , Indóis/química , Ratos , Tiazolidinas/químicaRESUMO
The necessity of avoiding the use of animals in vaccine potency testing has been widely recognized. The repeatability and reproducibility of the Expected Percentage of Protection (EPP) as a serological potency surrogate for A24 Cruzeiro foot-and-mouth disease virus (FMDV) strain was assessed, and compared with the results obtained with challenge in the Protection against Podal Generalization (PPG) test. To determine the EPPs, the serum titers obtained by liquid phase blocking competitive ELISA (lpELISA) and virus neutralization (VNT) in 10 potency trials using the same A24 Cruzeiro vaccine, were interpolated into previously validated logit transformation curves that correlate PPG with serology. Indirect serological assessment of vaccine matching between the serotype A FMDV strains A24 Cruzeiro and A/Argentina/01 was also carried out by lpELISA and VNT. The results obtained in this study strongly support the replacement of challenge tests for vaccine potency by indirect serological assays, at least for A24 Cruzeiro FMDV strain. While determination of EPPs by lpELISA titers showed an excellent repeatability, reproducibility and concordance with PPG for vaccine potency, assessments of cross-protection by VNT titers were more consistent with the PPG outcome.
Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Febre Aftosa/prevenção & controle , Testes de Neutralização/métodos , Vacinas Virais/imunologia , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Linhagem Celular , Cricetinae , Proteção Cruzada , Reprodutibilidade dos TestesRESUMO
O objetivo deste estudo foi avaliar a ocorrência de resposta compensatória no desempenho produtivo de juvenis de tilápia do Nilo Oreochromis niloticus, linhagem GIFT, submetidos a diferentes estratégias alimentares. Foram utilizados 135 juvenis de tilápia, distribuídos em nove tanques de polietileno de 100L cada. As estratégias testadas foram: grupo controle (alimentado todo dia), grupo alimentado por cinco dias seguidos de dois dias de restrição de alimento (5A/2R) e grupo alimentado por quatro dias seguidos de três dias de restrição de alimento (4A/3R). Foram avaliados parâmetros físico-químicos da água e de desempenho produtivo. Os resultados foram submetidos à análise de variância, e as médias foram comparadas pelo teste Tukey, a 5 por cento de probabilidade. A qualidade de água, o fator de condição e a conversão alimentar não foram influenciados pela estratégia alimentar. O grupo alimentado com a estratégia 5A/2R apresentou peso final, ganho de peso e taxa de crescimento específico semelhantes ao grupo continuamente alimentado (7,8 e 9,2g; 6,4 e 7,8g e 2,7 e 3,0 por cento dia-1, para peso final, ganho de peso e taxa de crescimento especifico, respectivamente). A estratégia 4A/3R apresentou os piores resultados de desempenho produtivo, e a estratégia 5A/2R pode ser usada na alimentação de juvenis de tilápia do Nilo sem prejuízo ao desempenho produtivo, possibilitando inclusive redução de até 22,5 por cento na quantidade de alimento ofertada.
The objective of this study was to evaluate the occurrence of compensatory answer on productive performance of Nile tilapia Oreochromis niloticus juveniles, GIFT line, submitted to different feeding strategies. It was used 135 juveniles tilapias distributed in nine 100L polyethylene tanks each. The tested strategies were the control group (fed everyday), group fed for 5 days followed by 2 days of food restriction (5A/2R) and group fed for 4 days followed by 3 days of food restriction (4A/3R). Were evaluated physical chemical water parameters e growth performance. Results were submitted to an analysis of variance and averages compared by Tukey test 5 percent. Water quality, condition factor and feed conversion were not influenced by feeding strategy. Group fed 5A/2R strategy showed final weight, weight gain and specific growth rate similar to group continually fed (7.8 e 9.2g; 6.4 e 7.8g e 2.7 e 3.0 percent day-1, for final weight, weight gain and specific growth rate, respectively). The strategy 4A/3R showed the poorest productive performance. Strategy 5A/2R can be used in Nile tilapia juveniles feeding without damage to the fish productive performance, allowing a reduction of up to 22.5 percent on the feed quantity offered.
RESUMO
Entacapone is indicated for clinical use as an adjunct to levodopalcarbidopa to treat patients with idiopathic Parkinson's Disease who experience the signs and symptoms of end-of-dose wearing-off. The aim of this study was to determine the photodegradation kinetics and to elucidate the structure of the main degradation product. The stability of entacapone was studied in order to investigate the degradation kinetics of this drug using LC as a stability indicator. Entacapone was subjected to accelerated photodegradation. This study was carried out with methanolic solutions, prepared from coated tablets, in quartz cells under UV light at 254 nm. The degradation process of entacapone in solutions can be described by second-order kinetics under the experimental conditions used in this study. The LC/MS/MS determinations revealed that in the above conditions the photodegraded product formed the geometric isomer of entacapone (Z-entacapone). The obtained results show the importance of appropriate light protection during the drug development process, storage, and handling.
Assuntos
Antiparkinsonianos/química , Catecóis/química , Nitrilas/química , Antiparkinsonianos/análise , Antiparkinsonianos/efeitos da radiação , Varredura Diferencial de Calorimetria , Catecóis/análise , Catecóis/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Isomerismo , Cinética , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Nitrilas/análise , Nitrilas/efeitos da radiação , Fotoquímica , Soluções , Espectrofotometria Infravermelho , Raios UltravioletaRESUMO
The objective of this study was to evaluate the occurrence of compensatory answer on productive performance of Nile tilapia Oreochromis niloticus juveniles, GIFT line, submitted to different feeding strategies. It was used 135 juveniles tilapias distributed in nine 100L polyethylene tanks each. The tested strategies were the control group (fed everyday), group fed for 5 days followed by 2 days of food restriction (5A/2R) and group fed for 4 days followed by 3 days of food restriction (4A/3R). Were evaluated physical chemical water parameters e growth performance. Results were submitted to an analysis of variance and averages compared by Tukey test 5%. Water quality, condition factor and feed conversion were not influenced by feeding strategy. Group fed 5A/2R strategy showed final weight, weight gain and specific growth rate similar to group continually fed (7.8 e 9.2g; 6.4 e 7.8g e 2.7 e 3.0% day-1, for final weight, weight gain and specific growth rate, respectively). The strategy 4A/3R showed the poorest productive performance. Strategy 5A/2R can be used in Nile tilapia juveniles feeding without damage to the fish productive performance, allowing a reduction of up to 22.5% on the feed quantity offered.
O objetivo deste estudo foi avaliar a ocorrência de resposta compensatória no desempenho produtivo de juvenis de tilápia do Nilo Oreochromis niloticus, linhagem GIFT, submetidos a diferentes estratégias alimentares. Foram utilizados 135 juvenis de tilápia, distribuídos em nove tanques de polietileno de 100L cada. As estratégias testadas foram: grupo controle (alimentado todo dia), grupo alimentado por cinco dias seguidos de dois dias de restrição de alimento (5A/2R) e grupo alimentado por quatro dias seguidos de três dias de restrição de alimento (4A/3R). Foram avaliados parâmetros físico-químicos da água e de desempenho produtivo. Os resultados foram submetidos à análise de variância, e as médias foram comparadas pelo teste Tukey, a 5% de probabilidade. A qualidade de água, o fator de condição e a conversão alimentar não foram influenciados pela estratégia alimentar. O grupo alimentado com a estratégia 5A/2R apresentou peso final, ganho de peso e taxa de crescimento específico semelhantes ao grupo continuamente alimentado (7,8 e 9,2g; 6,4 e 7,8g e 2,7 e 3,0% dia-1, para peso final, ganho de peso e taxa de crescimento especifico, respectivamente). A estratégia 4A/3R apresentou os piores resultados de desempenho produtivo, e a estratégia 5A/2R pode ser usada na alimentação de juvenis de tilápia do Nilo sem prejuízo ao desempenho produtivo, possibilitando inclusive redução de até 22,5% na quantidade de alimento ofertada.
RESUMO
The objective of this study was to evaluate the occurrence of compensatory answer on productive performance of Nile tilapia Oreochromis niloticus juveniles, GIFT line, submitted to different feeding strategies. It was used 135 juveniles tilapias distributed in nine 100L polyethylene tanks each. The tested strategies were the control group (fed everyday), group fed for 5 days followed by 2 days of food restriction (5A/2R) and group fed for 4 days followed by 3 days of food restriction (4A/3R). Were evaluated physical chemical water parameters e growth performance. Results were submitted to an analysis of variance and averages compared by Tukey test 5%. Water quality, condition factor and feed conversion were not influenced by feeding strategy. Group fed 5A/2R strategy showed final weight, weight gain and specific growth rate similar to group continually fed (7.8 e 9.2g; 6.4 e 7.8g e 2.7 e 3.0% day-1, for final weight, weight gain and specific growth rate, respectively). The strategy 4A/3R showed the poorest productive performance. Strategy 5A/2R can be used in Nile tilapia juveniles feeding without damage to the fish productive performance, allowing a reduction of up to 22.5% on the feed quantity offered.
O objetivo deste estudo foi avaliar a ocorrência de resposta compensatória no desempenho produtivo de juvenis de tilápia do Nilo Oreochromis niloticus, linhagem GIFT, submetidos a diferentes estratégias alimentares. Foram utilizados 135 juvenis de tilápia, distribuídos em nove tanques de polietileno de 100L cada. As estratégias testadas foram: grupo controle (alimentado todo dia), grupo alimentado por cinco dias seguidos de dois dias de restrição de alimento (5A/2R) e grupo alimentado por quatro dias seguidos de três dias de restrição de alimento (4A/3R). Foram avaliados parâmetros físico-químicos da água e de desempenho produtivo. Os resultados foram submetidos à análise de variância, e as médias foram comparadas pelo teste Tukey, a 5% de probabilidade. A qualidade de água, o fator de condição e a conversão alimentar não foram influenciados pela estratégia alimentar. O grupo alimentado com a estratégia 5A/2R apresentou peso final, ganho de peso e taxa de crescimento específico semelhantes ao grupo continuamente alimentado (7,8 e 9,2g; 6,4 e 7,8g e 2,7 e 3,0% dia-1, para peso final, ganho de peso e taxa de crescimento especifico, respectivamente). A estratégia 4A/3R apresentou os piores resultados de desempenho produtivo, e a estratégia 5A/2R pode ser usada na alimentação de juvenis de tilápia do Nilo sem prejuízo ao desempenho produtivo, possibilitando inclusive redução de até 22,5% na quantidade de alimento ofertada.
RESUMO
The selection of matching strains for use in outbreaks of foot-and-mouth disease (FMD) virus can be assessed in vivo or by serological r-value determination. Sera from animals involved in vaccine potency and cross-protection trials performed using the "Protection against Podal Generalization" (PPG) test for two serotype A strains were collected and analyzed by the virus neutralization test (VNT) and liquid-phase ELISA (lpELISA) in three laboratories. The average VNT r-values for medium and high serum titer classes from the A(24) Cruzeiro vaccinated animals were in line with the A/Arg/01 heterologous PPG outcome for all testing laboratories, suggesting that the vaccine strain A(24) Cruzeiro is unlikely to protect against the field isolate A/Arg/01. The corresponding lpELISA r-values were slightly higher and indicate a closer relationship between both strains. Pooling of serum samples significantly reduced the inter-animal and inter-trial variation. The results suggest that a suitable reference serum for vaccine matching r-value experiments might be a pool or a medium to high VNT or lpELISA titer serum. Furthermore, the VNT seems to produce the most reproducible inter-laboratory results. More work is, however, needed in order to substantiate these claims.
Assuntos
Vírus da Febre Aftosa/classificação , Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Febre Aftosa/virologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Argentina/epidemiologia , Bovinos , Reações Cruzadas , Surtos de Doenças , Ensaio de Imunoadsorção Enzimática , Febre Aftosa/epidemiologia , Imunoensaio/normas , Testes de NeutralizaçãoRESUMO
The stability of the broad-spectrum antibiotic meropenem was investigated in order to isolate and elucidate the mean degradation products involved in thermal and alkaline decomposition of meropenem in solution. The purification of thermal degradation product (45 degrees C) involved a combination of preparative chromatographic techniques. The degradates were characterized by NMR and ESI-MS. The thermal degradation product was a result of several chemical reactions, with modification of side chain and beta-lactam ring, resulting in a pyrrolic derivative. Under alkaline conditions (NaOH 0.1N), meropenem was converted totally to the corresponding beta-lactam ring-opened derivative, in sodium salt state. The degraded samples of meropenem reconstituted solution, powder for injection and alkaline solution was also studied in order to determine the preliminary cytotoxicity in vitro against mononuclear cells. The results obtained indicated that samples could be toxic in high concentration (2.0mg/mL) after 48h of incubation. The present study confirms the lability of the drug in aqueous solution, specially when submitted to thermal and alkaline conditions. Thus, it is necessary attention during the handling and storage of this antibiotic.